Cell Cycle Control 116. Tumor Suppressors Prevent Uncontrolled Cell Division. Regulation of the Cell Cycle: A Closer Look

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1 6 Cncer EV IE W O N LY Chpter 6.1 ctress ngelin Jolie crries cncer-cusing gene which puts her, nd some of her children, t high risk of getting cncer. Wht Is Cncer? Tumor Suppressors Prevent Uncontrolled Cell Division Tumors Cn e Cncerous isk Fctors for Cncer Pssing Genes nd Chromosomes to Dughter Cells 110 FO 6.2 Genes nd Chromosomes DN epliction 6.3 The Cell Cycle nd Mitosis 113 Cell Cycle Control 116 egultion of the Cell Cycle: Closer Look 6.5 Cncer Detection nd Tretment 118 Detection Methods: iopsy Tretment Methods: Chemotherpy nd dition 6.6 Meiosis 120 Interphse Meiosis I Meiosis II Crossing Over nd ndom lignment svvy reder lterntive Cncer Tretments 127 Sounds ight, ut Is It? 128 Interphse Mitosis Cytokinesis M06_OD9208_05_SE_C06.indd /13/14 3:42 PM

2 DN Synthesis, Mitosis, nd Meiosis Cncer is disese tht will ffect most people t some point in their lives. Of those who live n verge life spn, more thn one in three will e directly ffected with dignosis, nd those who escpe the disese themselves re likely to e ffected y the dignosis of loved one. Some types of cncer re geneticlly inherited, nd others re cquired during n individul s lifetime. ctress nd humnitrin Lifestyle chnges, like support those we love s they mke medicl decisions nd undergo quitting smoking, cn tretments. drmticlly ffect the risk of some cncers. ngelin Jolie s ttle ginst geneticlly inherited form of rest cncer led to her decision to hve oth of her rests surgiclly removed. Prior to his fll from grce, The origin of some cncers, Lnce rmstrong cquired testiculr like the one tht originted cncer, requiring the surgicl prior to Lnce rmstrong s n from competitive cycling for doping, cn e hrder to removl of one testicle. The difficult medicl choices fced y these individuls, while frightening to Understnding cncer cn help us tke etter cre of ourselves nd support loved explin. consider, cn serve s n impetus for ech of us to ttempt to etter understnd the iologicl sis of cncer. etter understnding of cncer cn help us to oth protect ourselves nd support those we love. Lifestyle chnges cn led to the prevention, delyed onset, or slowed progression of mny types of cncer. When cncer dignosis does occur, understnding the iologicl mechnisms of vrious tretments cn help us one with the dignosis. FO EVIEW ONLY 107

3 108 CHPTE 6 Cncer ml- mens d or evil. met- mens chnge or etween. Norml cell Norml cell division 6.1 Wht Is Cncer? Cncer is disese tht occurs when cell mkes copies of itself, or replictes, when it should not. Cell repliction occurs during cell division, process y which the originl prent cell divides to form two dughter cells. This process is regulted so tht cell divides only when more cells re required. Tumors Cn e Cncerous Unregulted cell division leds to pileup of cells tht form lump or tumor. tumor is mss of cells tht hs no pprent function in the ody. Tumors tht sty in one plce nd do not ffect surrounding structures re sid to e enign. Some enign tumors remin hrmless; others ecome cncerous. Invsive tumors, or those tht infiltrte surrounding tissues, re mlignnt cncers. Metstsis occurs when the cells of mlignnt tumor rek wy nd strt new cncers t distnt loctions (Figure 6.1). Cncer cells cn trvel virtully nywhere in the ody vi the lymphtic nd circultory systems. The lymphtic system collects fluid, clled lymph, lost from lood vessels. The lymph is then returned to the lood vessels, process tht lso llows cncer cells ccess to the loodstrem. Lymph nodes re structures tht filter fluids relesed from lood vessels. When cncer ptient is undergoing surgery, the surgeon will often remove few lymph nodes tht will e nlyzed for the presence of cncer cells. The presence of cncer cells in the nodes is n indiction tht some cells hve roken wy from the originl tumor nd might present elsewhere in the ody. One of the resons it ws so incredile tht Lnce rmstrong survived cncer ws tht the originl cncer in his testicle spred to his rin nd lungs. Metsttic cncers re much more difficult to tret thn cncers tht re detected efore they spred. isk Fctors for Cncer risk fctor is condition or ehvior tht increses the likelihood of developing disese. These risk fctors cn e impcted y genetics or environmentl exposures. Inherited Cncer isk. ngelin Jolie crries version of the C1 gene (for rest cncer susceptiility) tht mkes her five times more likely to get rest cncer thn other women. fter eing told tht she hd n 87% risk for rest cncer, she decided to undergo doule mstectomy procedure to remove oth of her Potentilly cncerous cell Tumor Unregulted cell division Mlignnt if tumor invdes surrounding tissue (cncerous) enign if tumor hs no effect on surrounding tissue (noncncerous) Metsttic if individul cells rek wy nd strt new tumor elsewhere (cncerous) FO EVIEW ONLY Figure 6.1 Wht is cncer? tumor is clump of cells with no function. Tumors my remin enign, or they cn invde surrounding tissues nd ecome mlignnt. Tumor cells my move, or metstsize, to other loctions in the ody. Mlignnt nd metsttic tumors re cncerous.

4 SECTION 6.1 Wht Is Cncer? 109 rests. The version of the gene tht she crries lso increses her risk for ovrin cncer the disese tht killed her mother. To eliminte her chnces of developing ovrin cncer, Jolie is plnning to hve her ovries removed s well. How did Jolie know her risks? ecuse severl memers of Jolie s fmily hd een dignosed with rest nd ovrin cncers, she ws tested for the presence of this gene. Since only out 1% of people crry this prticulr gene, unless severl immedite fmily memers hve een dignosed with cncer, this testing is not usully performed. Stop & Stretch round 12% of women will e dignosed with rest cncer t some point in their lifetime. If you took rndom smple of 1000 women, how mny would you predict would get rest cncer? If you took rndom smple of 1000 women with the C1 gene, how mny of them would you expect to get rest cncer? Environmentl Exposures. Exposure to prticulr sustnces, clled crcinogens, is correlted with development of prticulr cncers. For exmple, exposure to the humn ppillom virus (HPV) cn cuse nl nd orl cncer in femles nd mles, cervicl cncer in femles, nd penile cncer in mles. HPV-cused cncer risk cn e ll ut eliminted y vccintion; vccines re ville to oth mles nd femles. You cn lso limit your risk for HPV-cused cncers y limiting the numer of people you hve sex with nd y following sfer sex guidelines. Everyone knows tht smoking increses risk of cncer. Wht is less well known is tht smoking comined with excessive lcohol consumption increses cncer risk t greter level thn one would expect. This is ecuse some crcinogens enhnce the ctivity of other crcinogens. When this occurs, the sustnces involved re sid to e cting in synergistic mnner. Cigrette smoking nd lcohol consumption, two prctices commonly comined y college students, hve fr greter effect on cncer risk thn the sum of ech seprte risk fctor comined (Figure 6.2). Working with Dt Is the cncer risk ssocited with smoking nd drinking dditive or multiplictive? Explin your nswer. % of people dignosed with prticulr cncer Smokers Drinkers Smokers nd drinkers Figure 6.2 lcohol nd tocco re synergists. Smoking cigrettes while drinking is n unhelthy prctice. Lifestyle chnges, like quitting smoking, cn drmticlly ffect the risk of some cncers. FO EVIEW ONLY

5 110 CHPTE 6 Cncer Tle 6.1 Decresing Your Cncer isk While we hve seen tht exposures to prticulr gents cn increse risks of prticulr cncers, there re generl risk fctors tht increse risk of virtully every type of cncer. These include tocco use, excessive lcohol consumption, high-ft nd low-fier diet, lck of exercise, nd oesity (Tle 6.1). Limiting these exposures cn help prevent cncers from developing in our cells nd from eing pssed on to dughter cells produced when cells divide. isk-educing ehvior Specific isk eduction Informtion iologicl Mechnism of isk eduction Don t Use Tocco. Limit lcohol Consumption. Et Low-Ft, High-Fier Diet. Exercise egulrly. Mintin Helthy Weight. Figure 6.3 Why do cells divide? Cells divide in order to mke more cells. This cn llow n orgnism to grow (). Ech of us egins life s single fertilized egg cell tht underwent millions of rounds of cell division to produce ll the cells tht comprise the tissues nd orgns of our odies. Cells lso divide in order to hel wounds (). s this cut hels, new cells will replced those dmged y the injury. The use of tocco of ny type, whether delivered vi cigrettes, cigrs, pipes, or chewing tocco, increses your risk of mny cncers. Electronic cigrettes, which contin nicotine only, re new enough tht risks from their use hve not yet een determined. Men who wnt to decrese their cncer risk should hve no more thn two lcoholic drinks dy, nd women one or none. Et t lest 5 servings of fruits nd vegetles every dy s well s 6 servings of food from other plnt sources, such s reds, cerels, grins, rice, pst, or ens. Engge in physicl ctivity for t lest 30 minutes 5 dys week. void ecoming oese. If you re oese, consult physicin for weight loss progrm. Tocco nd tocco cigrette smoke contin more thn 20 known cncer-cusing sustnces. Chemicls present in tocco nd cigrette smoke hve een shown to increse cell division, dmge DN, inhiit cell s ility to repir dmged DN, nd prevent cells from dying when they should. When hrmful chemicls dissolve in lcohol, they re le to trverse cell memrnes nd cn dmge DN. Fruits nd vegetles re rich in ntioxidnts which help prevent DN dmge. Exercise keeps the immune system functioning effectively, llowing it to recognize nd destroy cncer cells. ecuse ftty tissues cn store hormones, the undnce of ftty tissue hs een hypothesized to increse the risk of hormone-sensitive cncers such s rest, uterine, ovrin, nd prostte cncer. () 6.2 Pssing Genes nd Chromosomes to Dughter Cells Cells hve evolved to divide for vriety of resons hving nothing to do with cncer. Cell division produces new cells to llow n orgnism to grow, to replce dmged cells, nd, in some cses, to reproduce (Figure 6.3). Some orgnisms reproduce y mking exct copies of themselves. eproduction of this type, clled sexul reproduction, results in offspring FO EVIEW ONLY () () ()

6 SECTION 6.2 Pssing Genes nd Chromosomes to Dughter Cells 111 () moe Visulize This () English ivy O N tht re geneticlly identicl to the originl prent cell. Single-celled orgnisms, such s cteri nd moe, reproduce in this mnner (Figure 6.4). Some multicellulr orgnisms cn reproduce sexully lso. For exmple, some plnts cn grow from clippings of stems, leves, or roots. eproduction from such cuttings is lso form of sexul reproduction (Figure 6.4). Orgnisms whose reproduction requires genetic informtion from two prents undergo sexul reproduction. Humns reproduce sexully when sperm nd egg cells ech contriute genetic informtion t fertiliztion. LY () If one moe divides one time, how mny offspring re produced? () If you removed one stem nd lef of the ivy plnt on this tree nd replnted it, would you expect it to grow into lrger stem nd lef or into two stems nd leves? Genes nd Chromosomes Figure 6.4 sexul reproduction. () This single-celled moe divides y copying its DN nd producing offspring tht re geneticlly identicl to the originl, prent moe. () Some multicellulr or gnisms, such s this English ivy plnt, cn reproduce sexully from cuttings. () Uncondensed DN EV IE W Whether reproducing sexully or sexully, ll dividing cells must first mke copy of their genetic mteril, the DN (deoxyrionucleic cid). DN crries the instructions, clled genes, for uilding ll of the proteins tht cell r equires. The DN in the nucleus is wrpped round proteins to produce s tructures clled chromosomes. Chromosomes re in n uncondensed, string-like form when cell is not prepring to divide (Figure 6.5). In order for cell division to occur, the DN in ech chromosome is compressed into more compct liner structure tht is esier to mneuver during cell division. Condensed chromosomes re less likely to ecome tngled or roken thn re the uncondensed nd string-like structures. Ech chromosome crries hundreds of genes. When chromosome is replicted, copy is produced tht crries those sme genes. The copied chromosomes, now clled sister chromtids, re ttched to ech other t region towrd the middle of the replicted chromosome, clled the centromere (Figure 6.5). ecuse the centromere is not lwys locted precisely in the center of the chromosome, it cn sudivide the chromosome into one long nd one short rm. Scientists hve mpped the loction of the C1 gene to the long rm of chromosome numer 17. & S t r e t c h If humns hve 23 pirs of chromosomes, ech crrying hundreds of genes, roughly how mny genes re there in the humn genome? FO Stop DN epliction During the process of DN repliction tht precedes cell division, the doulestrnded DN molecule is copied, first y splitting the molecule in hlf up the middle of the helix. New nucleotides re dded to ech side of the originl prent molecule, mintining the -to-t nd G-to-C se pirings. This process results in two dughter DN molecules, ech composed of one strnd of () DN condensed into chromosomes Centromere Figure 6.5 DN condenses during cell division. () DN in its replicted ut un condensed form prior to cell division. () During cell division, ech copy of DN is wrpped netly round mny smll proteins, forming the condensed structure of chromosome. fter DN repliction, two identicl sister chromtids re produced nd joined to ech other t the centromere. M06_OD9208_05_SE_C06.indd 111 Sister chromtids Chromosomes 10/13/14 3:42 PM

7 112 CHPTE 6 Cncer Visulize This ssume nother round of repliction were to occur to one of the hlf purple, hlf red DN molecules shown in prt (). How mny totl DN molecules would e produced? If the nucleotides eing dded to the newly synthesized strnd re purple, wht proportion of ech DN molecule would e purple? Figure 6.6 DN repliction. () DN repliction results in the production of two identicl dughter DN molecules from one prent molecule. Ech dughter DN molecule contins hlf of the prentl DN nd hlf of the newly synthesized DN. () The DN polymerse enzyme moves long the unwound helix, tying together djcent nucleotides on the newly forming dughter DN strnd. Free nucleotides hve three phosphte groups, two of which re cleved to provide energy for this rection efore the nucleotide is dded to the growing chin. Unduplicted chromosome Dupliction () DN repliction New strnds Prentl strnds Figure 6.7 Unduplicted nd duplicted chromosomes. n unreplicted chromosome is composed of one doule-strnded DN molecule. replicted chromosome is X-shped nd composed of two identicl doule-strnded DN molecules. Ech DN molecule of the duplicted chromosome is copy of the originl chromosome nd is clled sister chromtid. () The DN polymerse enzyme fcilittes repliction. DN polymerse Unwound DN helix DN polymerse Free nucleotides prentl nucleotides nd one newly synthesized strnd (Figure 6.6). ecuse ech newly formed DN molecule consists of one-hlf conserved prentl DN nd one-hlf new dughter DN, this method of DN repliction is referred to s semiconservtive repliction. eplicting the DN requires the ssistnce of enzymes, in prticulr, DN polymerse. The DN polymerse moves long the length of the unwound prentl DN strnd to fcilitte synthesis of the newly formed strnd (Figure 6.6). When free nucleotides floting in the nucleus hve n ffinity for ech other ( for T nd G for C), these complementry nucleotides ind to ech other cross the width of the helix nd then Centromere the DN polymerse ctlyzes the formtion of the covlent ond etween djcent Sister nucleotides long the length of the helix. chromtids When n entire chromosome hs een replicted, the newly synthesized sister chromtids re identicl to ech other nd ttched to ech other t the centromere (Figure 6.7). Duplicted The DN polymerse cn mke mistkes when fcilitting se piring. While chromosome uncommon, piring n with G for instnce, such mistkes cn lter the sequence of the originl gene. Chnges in the DN of gene re clled muttions. Normlly, repliction of the C1 gene produces n FO EVIEW ONLY

8 SECTION 6.3 The Cell Cycle nd Mitosis 113 exct copy of the gene. If mistkes in the copying occur, mutnt version of the gene cn e produced, which ppers to e the cse in the version of the gene tht ngelin Jolie crries. 6.3 The Cell Cycle nd Mitosis fter cell s chromosomes nd DN hve een replicted, the cell is le to undergo cell division nd produce dughter cells. One type of cell division, mitosis, is n sexul division tht produces two dughter cells tht re identicl to their originl prent cell nd to ech other. Mitosis occurs in the type of ody cells clled somtic cells. Somtic cells include ny cell type tht does not mito- mens thred. produce sex cells. In plnts, for exmple, the leves nd stem re composed of somtic cells nd undergo mitosis. The reproductive orgns of the plnt som- nd -some men ody. produce pollen nd egg cells, which re non-somtic cells clled sex cells. For cells tht divide y mitosis, the cell cycle includes three steps: (1) interphse, when the DN replictes; (2) mitosis, when the copied chromosomes split nd move into the dughter nuclei; nd (3) cytokinesis, when the cytoplsm of the prent cell splits (Figure 6.8). s you will see, interphse nd mitosis re further sudivided. cyto- nd -cyte relte to cells. Interphse -kinesis mens motion. norml cell spends most of its time in interphse (Figure 6.8). During this phse of the cell cycle, the cell performs its typicl functions nd produces the proteins required for the cell to do its prticulr jo. For exmple, during interphse, muscle cell produces proteins required for muscle contrction. Different cell types spend vrying mounts of time in interphse. Cells tht frequently divide, like skin cells, spend less time in interphse thn do those tht seldom divide, such s some nerve cells. cell tht will divide lso egins preprtions for division during interphse. Interphse cn e seprted into three phses: G 1, S, nd G 2. () Copying nd prtitioning DN Interphse DN is copied. Mitosis DN is split eqully into two dughter cells. Cytokinesis Prent cell is cleved in hlf. () Steps in the cell cycle Cell growth nd preprtion for division Second gp phse Mitosis Cell cycle FO EVIEW ONLY G 2 S M DN is copied. Interphse (G 1, S, G 2 ) First gp phse Cytokinesis G 1 Cell growth Figure 6.8 The cell cycle. () During interphse, the DN is copied. Seprtion of the DN into two dughter nuclei occurs during mitosis. Cytokinesis is the division of the cytoplsm, creting two dughter cells. () During interphse, there re two stges when the cell grows in preprtion for cell division, G 1 nd G 2 stges, nd one stge where the DN replictes, the S stge. The chromosomes re seprted nd two dughter cells re formed during the M phse.

9 114 CHPTE 6 Cncer During the G 1 (first gp or growth) phse, most of the cell s orgnelles uplicte. Consequently, the cell grows lrger during this phse. During the d S (synthesis) phse, the DN composing the chromosomes replictes. During the G2 (second gp) phse of the cell cycle, the cell continues to grow nd prepres for the division of chromosomes tht will tke plce during mitosis. LY S t o p & S t r e t c h If cell t G1 contins 4 picogrms of DN, how mny picogrms of DN will it contin t the end of the S phse of the cell cycle? Mitosis N The movement of chromosomes from the originl prent cell into two dughter cells occurs during mitosis. Whether these phses occur in n niml or plnt, the outcome of mitosis nd the next phse, cytokinesis, is the sme: O Mitosis nd Cytokinesis G2 Cell Cycle W M G1 IE Mitosis S Pole Interphse se E Centriole EV h terp f In nd o Nucler envelope Centrioles eplicted uncondensed DN FO Nucleus M06_OD9208_05_SE_C06.indd 114 Cell memrne DN hs lredy replicted ut hs not yet condensed into chromosomes. Microtuules Centromere Pole Chromosomes (ech pir of sister chromtids joined together t centromere) Metphse se Proph DN condenses into chromosomes. Microtuules form nd re nchored y centrioles. The nucler envelope egins to rek down. Chromosomes lign t the middle of the cell etween the two poles. The microtuules grow long enough to ttch to the chromosomes t their centromeres. 10/13/14 3:42 PM

10 SECTION 6.3 The Cell Cycle nd Mitosis 115 W esis Cytokin O N LY the production of geneticlly identicl dughter cells. To chieve this telo- mens end or completion. outcome, the sister chromtids of replicted chromosome re pulled prt, nd one copy of ech is plced into ech newly forming nucleus. Mitosis is ccomplished during four stges: prophse, metphse, nphse, nd t elophse. Figure 6.9 summrizes the cell cycle in niml cells. The four stges of mitosis re nerly identicl in plnt cells. During prophse, the replicted chromosomes condense, llowing them to move round in the cell without ecoming entngled. Protein structures clled microtuules lso form nd grow, ultimtely rditing out from opposite ends, or poles, of the dividing cell. The growth of microtuules helps the cell to expnd. Motor proteins ttched to microtuules lso help pull the chromosomes round during cell division. The memrne tht surrounds the nucleus, clled the nucler envelope, reks down so tht the microtuules cn gin ccess to the replicted chromosomes. t the poles of ech dividing niml cell, nphse g n ni n egi egi nnin te of In g of se rph Inte rph se EV IE Microtuules FO middle of oles. The ugh to t their The microtuules contrct nd seprte the sister chromtids from ech other, pulling them towrd the two poles of the cell. Teloph se nd Cyto kinesis During telophse, nucler envelopes re-form nd chromosomes decondense. During cytokinesis in n niml cell, nd of filments contrcts round the equtor of the cell, cusing two cells to form from the originl prent cell. The two dughter cells enter G1 phse of interphse. Figure 6.9 Cell division in niml cells. This digrm illustrtes how cell division pro ceeds from interphse through mitosis nd cytokinesis. M06_OD9208_05_SE_C06.indd /13/14 3:42 PM

11 116 CHPTE 6 Cncer () Cytokinesis in n niml cell () Cytokinesis in plnt cell Cell plte nd of microfilments Figure 6.10 comprison of cytokinesis in niml nd plnt cells. () niml cells produce nd of filments tht tightens like elt to pinch the cell in hlf. () Plnt cells form cell plte down the middle of the prent cell tht gives rise to the cell wll. structures clled centrioles physiclly nchor one end of ech forming microtuule. Plnt cells do not contin centrioles, ut microtuules in these cells do remin nchored t pole. During metphse, the replicted chromosomes re ligned cross the middle, or equtor, of ech cell. To do this, the microtuules, which re ttched to ech chromosome t the centromere, line up the chromosomes in single file cross the middle of the cell. During nphse, the centromere splits, nd the microtuules shorten to pull ech sister chromtid of chromosome to opposite poles of the cell. In the lst stge of mitosis, telophse, the nucler envelopes re-form round the newly produced dughter nuclei, nd the chromosomes revert to their uncondensed form. Cytokinesis Cytokinesis is the division of the cytoplsm tht tkes plce directly fter telophse. During cytokinesis in niml cells, nd of proteins encircles the cell t the equtor nd divides the cytoplsm. This nd of proteins contrcts to pinch prt the two nuclei nd the surrounding cytoplsm, creting two dughter cells from the originl prent cell. Cytokinesis in plnt cells requires tht cells uild new cell wll, n inflexile structure surrounding the plnt cells. Figure 6.10 shows the difference etween cytokinesis in niml nd plnt cells. During telophse of mitosis in plnt cell, memrne-ound vesicles deliver the mterils required for uilding the cell wll to the center of the cell. These mterils include tough, firous crohydrte clled cellulose s well s some proteins. The memrnes surrounding the vesicles gther in the center of the cell to form structure clled cell plte. The cell plte nd forming cell wll grow cross the width of the cell nd form rrier tht eventully seprtes the products of mitosis into two dughter cells. fter cytokinesis, the cell reenters interphse, nd if the conditions re fvorle, the cell cn divide gin. ny tissue tht undergoes mitotic cell division cn give rise to tumor if cell egins to divide when it should not. Tht tumor cn increse in size if cell division remins uncontrolled. 6.4 Cell Cycle Control When cell division is working properly, it is tightly controlled process nd tumor formtion is prevented. Even if one renegde cell escpes these regultory controls nd forms tumor, mechnisms re in plce to get rid of the tumor. How is such regultion ccomplished? Tumor Suppressors Prevent Uncontrolled Cell Division FO EVIEW ONLY Cells do not simply proceed through the cell cycle from strt to finish. Insted, proteins re continuously surveying cells to mke sure tht, mong other things, the DN hs een replicted properly. Proteins clled tumor suppressors inspect newly replicted DN. If it is dmged in ny wy, for exmple, if G:T se pir exists, the cell does not continue the process of cell division. The norml C1 gene encodes protein tht functions s tumor suppressor. The mutnt version of the C1 gene tht ngelin Jolie inherited is not le to crry out this function. Therefore, cells where this mutnt gene is expressed (i.e., cells composing rest nd ovrin tissues), could divide more thn they re supposed to. If this hppens, tumors cn form (Figure 6.11).

12 SECTION 6.4 Cell Cycle Control 117 Muttions to tumor-suppressor genes DN Protein Tumor suppressor Muttion Tumor-suppressor protein stops tumor formtion y suppressing cell division. Mutted tumor suppressor egultion of the Cell Cycle: Closer Look Muttion Mutted tumorsuppressor protein fils to stop tumor growth. Tumor suppressors re not the only proteins gurding checkpoints. fter every mjor event in the cell cycle, dditionl proteins determine whether the cell should e llowed to continue through the cell cycle (Figure 6.12). t the G 1 checkpoint, proteins check to determine if the cell hs grown enough to e le to sudivide into two dughter cells. fter the DN hs undergone repliction during the S phse, the success of tht repliction is ssessed t the G 2 checkpoint. Lte in the M phse, proteins t the third checkpoint doule check tht ech chromosome is present in the proper duplicted configurtion nd ttched to microtuule. G 2 checkpoint Ws DN replicted correctly? G 2 Cell cycle S M Metphse checkpoint re ll the chromosomes ttched to microtuules? G 1 G 1 checkpoint Is cell division necessry? Is the cell lrge enough for G 2? The proteins tht prticipte in this regultion re coded for cell cycle control genes tht we ll crry. These cell cycle genes, clled proto-oncogenes (proto mening efore, nd onco mening cncer) cn give rise to cncercusing oncogenes if they re mutted. Proto-oncogenes encode proteins tht stimulte cell division when conditions re right. Oncogenes stimulte cell division when they should not (Figure 6.13, on the next pge). proto- mens efore. Proto-oncogenes nd tumor suppressors work together to fcilitte the pssge of helthy cells, nd to impede the pssge of dmged cells, onco- mens cncer. through cellulr checkpoints. Figure 6.11 Muttions to tumorsuppressor genes. Muttions to tumor-suppressor genes cn increse the likelihood of cncer developing. Visulize This t which checkpoint will cell tht hs een treted with chemicl tht prevents microtuule formtion e stopped? Figure 6.12 Controls of the cell cycle. Checkpoints t G 1, G 2, nd metphse determine whether cell will e llowed to divide. FO EVIEW ONLY

13 118 CHPTE 6 Cncer Closer Look, continued C1 (norml) C U T I O N hnge in owel or ldder hits sore tht does not hel nusul leeding or dischrge hickening or lump ndigestion or difficulty swllowing vious chnge in wrt or mole gging cough or horseness Figure 6.14 Wrning signs of cncer. Self-screening for cncer cn sve your life. If you experience one or more of these wrning signs, see your doctor. C1 (mutnt) Figure 6.13 The norml version of the C1 gene leds to controlled cell division. The mutnt version of C1 is unle to perform this jo. Stop & Stretch Our current understnding of how cncers rise is sometimes clled the multiple hit model of crcinogenesis. sed on your understnding of how cncers rise, descrie wht the phrse multiple hit mens. Most of us will inherit few, if ny, mutnt cell-cycle control genes. Insted, our level of exposure to environmentl risk fctors will determine whether enough muttions will ccumulte during our lifetime to cuse cncer. This is why cncer is more common in the elderly. Older people hve tissues tht hve undergone more cell division nd cells tht hve een exposed to more crcinogens, leding to incresed likelihood of muttion to genes controlling the cell cycle. 6.5 Cncer Detection nd Tretment When cncers re detected nd treted erly, their progression cn e hlted nd the odds of survivl increse. eing on the lookout for wrning signs (Figure 6.14) cn help lert individuls tht cncer is developing. Detection Methods: iopsy Mny cncers re first detected when lump is discovered either y self-exmintion or during medicl exm. Once lump hs een discovered, physicin might perform iopsy to surgiclly remove nd nlyze some of the cells. If the lump is composed of fluid, not cells, it is most likely enign cyst. Cysts cn rise in response to hormones or inflmmtion cused y injury. They do not progress to cncers nd often go wy without ny form of tretment. When solid mss of cells is found, the cells cn e viewed under microscope. enign tumors consist of orderly growths of cells tht resemle the cells of the tissue from which they were tken. Mlignnt or cncerous cells do not resemle other cells found in the sme tissue; they divide so rpidly tht they do not hve time to produce ll the proteins necessry to uild norml cells, which leds to n norml ppernce tht trined technicin cn identify. Since ngelin Jolie chose to hve her rests removed efore cncer developed, she did not hve to e concerned out whether the cncer hd spred nd there ws no reson to undergo further tretment. FO EVIEW ONLY

14 SECTION 6.5 Cncer Detection nd Tretment 119 Tretment Methods: Chemotherpy nd dition Unfortuntely, iopsy of Lnce rmstrong s tumor showed tht it ws cncerous, nd susequent tests showed tht the cncer hd spred. The dy fter his cncer dignosis, Lnce rmstrong hd one testicle surgiclly removed. ecuse the cncer hd spred, he lso underwent chemotherpy nd rdition. Chemotherpy. During chemotherpy, chemicls tht selectively kill dividing cells re injected into the loodstrem. ecuse cncer is disese cused y muttions, some cncer cells crry muttions tht will llow them to e resistnt to vrious chemotherpeutic gents. Therefore, treting cncer ptient with comintion of chemotherpeutic gents imed t different cell cycle events increses the chnces of destroying ll the cncerous cells in tumor. For exmple, some chemotherpeutic gents prevent the chromosomes from eing pulled to the equtor during cell division nd others prevent DN synthesis. Unfortuntely, norml cells tht divide rpidly cn lso e ffected y chemotherpy. Hir follicles, cells tht produce red nd white lood cells, nd cells tht line the intestines nd stomch re often dmged or destroyed. The effects of chemotherpy therefore include temporry hir loss (Figure 6.15), nemi (dizziness nd ftigue due to decresed numers of red lood cells), nd lowered protection from infection due to decreses in the numer of white lood cells. In ddition, dmge to the cells of the stomch nd intestines cn led to nuse, vomiting, nd dirrhe. EVIEW dition Therpy. fter tumor is surgiclly removed, there is lwys chnce tht some cncer cells from the tumor were not excised nd remin in the ody. dition therpy is the use of high-energy prticles imed t the loction of the tumor in n effort to kill ny cncer cells tht might remin. This therpy is typiclly used only when cncers re locted close to the surfce of the ody ecuse it is difficult to focus em of rdition on internl orgns nd tissue dmge cn e quite severe. ecuse testicle cn e removed in its entirety, rdition therpy is usully not necessry for men with testiculr cncer, like Lnce rmstrong. However, the cncer tht hd spred to his rin would normlly hve een suject to rdition tretment. It is very difficult for surgeon to remove rin tumor without ffecting surrounding tissues or leving some cncer cells ehind. ecuse he ws still llowed to prticipte in professionl cycling events, nd ecuse he fered tht rdition to his rin would ffect his lnce nd ility to ride ike, Lnce rmstrong chose not to undergo rdition therpy on the tumors tht metstsized to his rin. He hoped tht surgicl removl nd chemotherpy would kill those cncer cells. Stop & Stretch One risk of rdition therpy is n incresed likelihood of new tumors emerging 5 to 15 yers lter. Why might this tretment increse risk?fo cncer Figure 6.15 Chemotherpy. Chemotherpy cused Lnce rmstrong to lose his hir. Understnding cncer cn help us tke etter cre of ourselves nd help support loved one with the dignosis. ONLY ngelin Jolie crries gene tht incresed her risk of cncer. Could she pss tht risk on to her children? Wht out Lnce rmstrong? t the time of his dignosis, he did not hve children ut now he hs five. re they t incresed risk of cncer ecuse he underwent cell-dmging chemotherpy prior to their irth? n understnding of the type of cell division tht produces sperm nd eggs will help you nswer these questions.

15 120 CHPTE 6 Cncer Homologous pir of chromosomes Centromere C Two lleles of the sme gene Figure 6.16 homologous pir of chromosomes. Homologous pirs of chromosomes hve the sme genes (shown here s,, nd C) ut my hve different lleles. The dominnt llele is represented y n uppercse letter, while the recessive llele is shown with the sme letter in lowercse. Note tht the chromosomes of homologous pir ech hve the sme size, shpe, nd positioning of the centromere. meio- mens to mke smller. c 6.6 Meiosis Meiosis is form of cell division tht produces specilized cells clled gmetes tht contin hlf the numer of chromosomes of the prent cell. Gmetes re produced only within the gonds, or sex orgns. In humns, the mle gonds re testes, nd the femle gonds re ovries. The mle gmetes re clled sperm cells, femle re clled egg cells. ecuse humn somtic cells hve 46 chromosomes nd meiosis reduces tht numer y hlf, the gmetes produced during meiosis contin 23 chromosomes ech. Chromosomes in somtic cells occur in pirs. The 46 chromosomes in humn somtic cells re ctully 23 different pirs of chromosomes. In somtic cells, one memer of ech pir ws inherited from the mother nd one from the fther. The memers of homologous pir of chromosomes re the sme size nd shpe nd crry the sme genes, lthough not necessrily the sme versions (Figure 6.16). Different versions of the sme gene re clled lleles of gene. We hve seen tht there re different versions of the C1 gene. The norml version of the gene helps control the cell cycle, while mutnt version does not. kryotype is highly mgnified photogrph of the chromosomes, rrnged in pirs. The 46 humn chromosomes cn e rrnged into 22 pirs of nonsex chromosomes, or utosomes, nd one pir of sex chromosomes (the X nd Y chromosomes) to mke totl of 23 pirs. Humn mles hve n X nd Y chromosome, while femles hve two X chromosomes (Figure 6.17). Once meiosis is completed, there is one copy of ech chromosome (1 23) in every gmete. When only one memer of ech homologous pir Visulize This Which sex chromosome is lrger nd therefore crries more genetic informtion? utosomes (22 pirs) Sex chromosomes (1 pir) Femle FO EVIEW ONLY X Mle or X Figure 6.17 Kryotype. The pirs of chromosomes in this kryotype re rrnged in order of decresing size nd numered from 1 to 22. The X nd Y sex chromosomes re the 23rd pir. X Y

16 SECTION 6.6 Meiosis 121 Spermproducing cells in the testes hve 46 chromosomes (23 pirs). Figure 6.18 Gmete production. The diploid cells of the ovries nd testes undergo meiosis nd produce hploid gmetes. When fertiliztion occurs, the diploid condition is restored. is present in cell, we sy tht the cell is hploid (n) oth egg cells nd sperm cells re hploid. fter the sperm nd egg fuse, the fertilized cell, or zygote, will contin two sets of chromosomes nd is sid to e diploid (2n) (Figure 6.18). Like mitosis, meiosis is preceded y n interphse stge tht includes G 1, S, nd G 2. Interphse is followed y two phses of meiosis, meiosis I nd meiosis II, in which divisions of the nucleus tke plce ( Figure 6.19). Meiosis I seprtes the memers of homologous pir from ech other. Meiosis II seprtes the chromtids from ech other. oth meiotic divisions re followed y cytokinesis, during which the cytoplsm is divided etween the resulting dughter cells. Interphse Diploid (2n) The interphse tht precedes meiosis consists of G 1, S, nd G 2. This interphse of meiosis is similr in most respects to the interphse tht precedes mitosis. The centrioles from which the microtuules will originte re present. The G phses re times of cell growth nd preprtion for division. The S phse is when DN repliction occurs. Once the cell s DN hs een replicted, it cn enter meiosis I. Egg-producing cells in the ovry hve 46 chromosomes (23 pirs). Meiosis Meiosis Hploid (n) Egg cell hs 23 chromosomes (unpired). Sperm cell hs 23 chromosomes (unpired). Cell growth nd preprtion for division G 2 Fertiliztion Meiosis I fter mny rounds of mitosis Zygote hs 46 chromosomes (23 homologous pirs). S Meiosis II Interphse nd Meiosis Diploid (2n) Diploid y Figure 6.19 Interphse nd meiosis. Interphse consists of G 1, S, nd G 2 nd is followed y two rounds of nucler division, meiosis I nd meiosis II. G 1 End of previous mitotic event Cell growth FO EVIEW ONLY DN is copied. Interphse (G 1, S, G 2 ) S nd G phses similr to the S nd G phses of mitosis

17 122 CHPTE 6 Cncer Prophse I Nucler envelope strts to rek down. Microtuules strt to ssemle. DN condenses into chromosomes. Meiosis I Meiosis II se Interph Diploid eplicted Centrioles uncondensed DN Nucler envelope Microtuules DN is replicted during S phse of interphse. O Metphse Homologous chromosomes lign t middle of cell. EV G1 IE Cell memrne Nucleus W Crossing over my occur. G2 ndom lignments N End of Meiosis I LY Interphse nd Meiosis (G1, S1, G2) nphse Homologous chromosomes re seprted y shortening of microtuules. S Visulize This There is short interphse etween meiosis I nd meiosis II. Look t the structure of chromosomes s they leve meiosis I nd gin t prophse II. Does DN dupliction occur during the interphse preceding meiosis II? Figure 6.20 Meiosis. This digrm illustrtes interphse, meiosis I, meiosis II, nd cytokinesis in n niml cell. FO Meiosis I M06_OD9208_05_SE_C06.indd 122 The first meiotic division, meiosis I, consists of prophse I, metphse I, nphse I, nd telophse I (Figure 6.20). During prophse I of meiosis, the nucler envelope strts to rek down, nd the microtuules egin to ssemle. The previously replicted chromosomes condense so tht they cn e moved round the cell without ecoming entngled. The condensed chromosomes cn e seen under microscope. t this time, the homologous pirs of chromosomes exchnge genetic informtion in process clled crossing over, which will e explined in moment. t metphse I, the chromosomes line up t the equtor, ut they do so in homologous pirs. This is the key difference etween meiosis nd mitosis, where the chromosomes lign single file t the equtor. Homologous pirs re rrnged ritrrily regrding which memer fces which pole. This process is clled rndom lignment. t the end of this section, you will find detiled descriptions of crossing over nd rndom lignment long with their impct on genetic diversity. t nphse I, the homologous pirs re seprted from ech other y the shortening of the microtuules, nd t telophse I, nucler envelopes reform round the chromosomes. DN is then prtitioned into ech of the two 10/13/14 3:42 PM C

18 SECTION 6.6 Meiosis Prophse II Microtuules lengthen. Meiosis II 123 nphse II Sister chromtids re seprted y shortening of microtuules. Cytokinesis IE W O N LY Cytokinesis Hploid Metphse II Chromosomes lign t middle of cell. EV Telophse I nd Cytokinesis Cytokinesis results in two dughter cells. Nucler envelopes re-form. Telophse II nd Cytokinesis Four hploid dughter cells result. Nucler envelopes re-form. dughter cells y cytokinesis. ecuse ech dughter cell contins only one copy of ech memer of homologous pir, t this point the cells re hploid. Now oth of these dughter cells re redy to undergo meiosis II. Stop & Stretch How is meiosis I similr to mitosis? How is it different? FO ing Meiosis II Meiosis II consists of prophse II, metphse II, nphse II, nd telophse II. This second meiotic division is virtully identicl to mitosis nd serves to seprte the sister chromtids of the replicted chromosome from ech other. t prophse II of meiosis, the cell is redying for nother round of division, nd the microtuules re lengthening gin. t metphse II, the chromosomes lign in single file cross the equtor in much the sme wy tht they do during mitosis. t nphse II, the sister chromtids seprte from ech other nd move to opposite poles of the cell. t telophse II, the seprted chromosomes ech ecome enclosed in their own nucleus. Ech individul cn produce millions of different types of gmetes due to two events tht occur during meiosis I crossing over nd rndom lignment. M06_OD9208_05_SE_C06.indd /13/14 3:42 PM

19 124 CHPTE 6 Cncer () If crossing over does not occur in prophse I ed flowers Long grins () If crossing over does occur in prophse I L I r r L I L oth of these processes gretly increse the numer of different kinds of gmetes tht n individul cn produce nd therefore increse the vrition in individuls tht cn e produced when gmetes comine. Crossing Over nd ndom lignment Crossing over occurs during prophse I of meiosis I. It involves the exchnge of portions of chromosomes from one memer of homologous pir to the other memer. Crossing over cn occur severl times on ech homologous pir during ech occurrence of meiosis. To illustrte crossing over, consider n exmple using genes involved in the production of flower color nd pollen shpe in sweet pe plnts. These two genes re on the sme chromosome nd re clled linked genes. Linked genes move together on the sme chromosome to gmete, nd they my or my not undergo crossing over. If pe plnt hs red flowers nd long pollen grins, the chromosomes my pper s shown in Figure It is possile for this plnt to produce four different types of gmetes with respect to these two genes. Two types of gmetes would result if no crossing over occurred etween these genes the gmete contining the red flower nd long pollen chromosome nd the gmete contining the white flower nd short pollen chromosome. Two dditionl types of gmetes could e produced if crossing over did r L I L r I I L r r I White flowers Short grins Meiosis Meiosis Two types of gmetes Four types of gmetes FO EVIEW ONLY I L r L L r r I I L r I Crossing over Figure 6.21 Crossing over. If flower with the ove rrngement of lleles undergoes meiosis, it cn produce () two different types of gmetes for these two genes if crossing over does not occur or () four different types of gmetes for these two genes if crossing over occurs t L.

20 SECTION 6.6 Meiosis 125 occur one type contining the red flower nd short pollen grin chromosome nd the other type contining the reciprocl white flower nd long pollen grin chromosome. Therefore, crossing over increses genetic diversity y incresing the numer of distinct comintions of genes tht my e present in gmete. ndom lignment of homologous pirs lso increses the numer of geneticlly distinct types of gmetes tht cn e produced. The rrngement of homologous pirs of chromosomes t metphse I determines which chromosomes will end up together in gmete. If we consider only two homologous pirs of chromosomes, then two different lignments re possile, nd four different gmetes cn e produced. s the numer of chromosomes in n orgnism s genome increses, so does the numer of possile lignments nd the numer of geneticlly distinct gmetes tht orgnism cn produce (Figure 6.22). ndom lignment does not occur during mitosis, ecuse the chromosomes lign single file cross the equtor in order to produce identicl dughter Visulize This The cell elow hs two homologous pirs. How mny different lignments re possile with three homologous pirs of chromosomes? () One possile metphse I lignment Mternl Pternl Meiosis () nother possile metphse I lignment Meiosis Two comintions of chromosomes in gmetes These gmetes contin only chromosomes this orgnism inherited from its mother. These gmetes contin only chromosomes this orgnism inherited from its fther. Two dditionl comintions of chromosomes in gmetes These gmetes contin one mternl nd pternl chromosome. FO EVIEW ONLY Figure 6.22 ndom lignment. In this exmple, the orgnism undergoing meiosis hs only four chromosomes. The orgnism inherited the lue chromosomes from its fther nd the red chromosomes from its mother. When there re two homologous pirs of chromosomes, two possile lignments, () nd (), cn occur. These different lignments cn led to novel comintions of genes in the gmetes.

21 126 CHPTE 6 Cncer Prophse Metphse nphse Telophse (sister chromtids seprte) cells. For summry of the differences etween mitosis nd meiosis, see Figure Now tht you hve cler understnding of cell division, we cn turn our ttention to the question of whether people cn pss cncer on to their children. In the cses of ngelin Jolie nd Lnce rmstrong, the nswer to tht question will differ. Genetic testing showed tht ngelin Jolie inherited the C1 gene from her mother. Typiclly, it tkes more thn one muttion to cuse cncer, ut this prticulr muttion of the C1 will cuse rest or ovrin cncer in the vst mjority of women tht crry the gene. Since Jolie inherited one mutnt version of the C1 gene, she cn produce egg cells crrying the mutnt version or the norml version. Therefore, ech of her iologicl children dughters Shiloh nd Vivienne nd son Knox hs 50% chnce of crrying the mutnt version of this gene. If they did inherit the mutnt Mitosis Two diploid dughter cells tht re oth geneticlly identicl to the originl prent cell DN repliction Chromosomes lign long the equtor. Diploid prent cell Prophse I Metphse I Homologues lign s pirs. DN repliction nphse I Telophse I (memers of ech homologous pir seprte) Dughter cells re hploid (hve hlf s mny chromosomes s the prent cell). Meiosis I FO EVIEW ONLY Meiosis II (sister chromtids seprte) Figure 6.23 Compring mitosis nd meiosis. Mitosis is type of cell division tht occurs in somtic cells nd gives rise to dughter cells tht re exct genetic copies of the prent cell. Meiosis occurs in cells tht will give rise to gmetes nd decreses the chromosome numer y one-hlf. Ech gmete receives one memer of ech homologous pir.

22 Svvy eder 127 version of the gene, Jolie s dughters re t incresed risk of rest nd ovrin cncer nd her son is t incresed risk of rest nd prostte cncer. ny of her iologicl children who did not receive the mutnt version of the C1 gene hve cncer risk tht is equl to tht of their dopted silings Mddox, Zhr, nd Px, ssuming tht they didn t inherit the mutnt version from their iologicl prents. The cuses of Lnce rmstrong s cncer re not s cler-cut s Jolie s genetic predisposition. His fmily history of cncer is not nerly s pronounced s hers, so his cncer could hve developed in response to some comintion of inherited muttions nd muttions cused y crcinogens he ws exposed to during his lifetime. When it comes to cncer risk in children of those dignosed with cncer, there is lso concern out muttions cused y chemotherpy. When chemotherpeutic gents injure somtic cells, tht dmge is not trnsmissile to offspring. However, if the chemotherpy dmges cells tht undergo meiosis to produce sperm, muttions could e pssed to children. ecuse of this risk, rmstrong stored sperm in sperm nk efore undergoing chemotherpy. Of his five children, three with his first wife were conceived with sperm stored efore his surgery nd chemotherpy, nd two with his current wife were conceived nturlly. ecuse the specific cuse of Lnce rmstrong s cncer is not known, it is not possile to determine the risk of cncer for ny of his five children. Likewise, it is not possile to determine whether the two children orn fter his chemotherpy re t incresed risk since we don t know whether the sperm involved in their conception crried chemotherpy- dmged, cell-cycle, control genes. Therefore, for ny children tht rmstrong (or ny of us) might hve, the comined effects of inherited mutnt lleles nd ny muttions induced y environmentl exposures in conjunction with lifestyle fctors will determine whether nd when cncers my develop. One wesite clims tht 80% of cncer therpies re locked y the ptient s emotions nd tht these locks cn e removed y technique clled tpping. Just downlod the file, follow the tpping instructions, nd you will feel etter in no time. nother wesite clims tht shrks do not get cncer nd tht tking shrk-crtilge supplements cn help tret cncer in humns. In study of the effectiveness of shrk crtilge, the study uthors report tht 15 of 29 ptients dignosed with terminl cncer were still live one yer fter eginning to tke the supplements, which is remrkle result y ny mesure, ccording to the study uthors. Wesites for lterntive cncer tretment centers offer unproven tretments to ptients tht cost tens of thousnds of dollrs nd re not covered y insurnce. ccording to dvertisements, these tretments re often supervised y medicl doctors. The sites re filled with testimonils, ut no dt, out the effectiveness of such tretments. 1. The wesite tht suggested tht emotions cn lock cncer therpies presented no evidence to ck up this clim. Wht would you do if you wnted to know whether tht clim hd ny merit? 2. The study on shrk crtilge ws pulished in non-peer reviewed journl. Does this fct dd or sutrct from the crediility of this rticle? Why? Some types of cncer re geneticlly inherited, nd others re cquired during n individul s lifetime. lterntive Cncer Tretments FO EVIEW ONLY

23 128 CHPTE 6 Cncer Sounds ight ut is it? tnning slon locted ner cmpus gives 20% discount to students. Two girls on your dorm floor hve een using the tnning eds. When you question the sfety of this prctice, your friends clim tht eing exposed to 20 minutes of ultrviolet light from tnning eds is ctully sfer thn eing in the sun for few hours. When you point out tht tnning eds cn cuse skin cncer, they sy tht most slons hve switched to uls tht hve only one kind of ultrviolet light, mking them much sfer thn efore. They lso clim tht using tnning eds mkes them look nd feel more helthful, in prt ecuse using tnning eds helps them to get the recommended mount of vitmin D. The use of tnning eds is not only sfe, it improves helth. Sounds right, ut it isn t. 3. Wht other informtion do you need to determine whether the one-yer survivl rte of the shrk crtilge study hs ny rel mening? 4. Would the fct tht the uthor of the shrk crtilge study owns compny tht sells the product mke you more or less skepticl of his findings? Wht out the fct tht shrks ctully do get cncer? 5. While most medicl doctors hve dedicted their lives to helping people in need, few will promote products nd services simply to mke money. Should you lwys elieve the word of someone with n dvnced degree? 6. Why do you think tht so mny people fll prey to duious cncer cures? 1. Even if there were evidence tht tnning for 20 minutes ws sfer thn eing in the sun for few hours, would this provide evidence tht tnning eds re sfe? Why or why not? 2. Ultrviolet light (UV) from the sun occurs in two different DN wvelengths, longer UV rys nd shorter UV rys. UV rys cuse the surfce of the skin to urn while the longer UV rys penetrte further into the skin. Erly tnning eds used UV uls, ut most hve now switched to UV uls. From n economic stndpoint, why might it enefit tnning ed mnufcturers nd slon owners to switch to UV? 3. When light-skinned people re exposed to dmging levels of UV light, their skin temporrily drkens in n ttempt to prevent further dmge from occurring. (Drk-skinned people hve nturlly high levels of pigments in the skin, n evolutionry dpttion tht occurred when their ncestors were living in geogrphic rnge with high UV light exposure.) tn in light-skinned people is evidence tht the skin hs een injured. Should tn in light-skinned people e considered evidence of good helth? 4. While sunlight is required for the ody to synthesize vitmin D, the mericn Cncer Society recommends tht no one e exposed to more thn 15 minutes of sunlight efore pplying sunscreen. If you wnted to ensure tht you were getting enough vitmin D without exposing yourself to ultrviolet light from ny source, wht could you do? 5. Consider your nswers to questions 1 4 nd explin why the originl sttement olded ove sounds right, ut isn t. FO EVIEW ONLY