Document EMG3VLbM4RVM9rdRGjwMMZ1g

Fob-26-2001 09:24am F r d U P P LIBRARY +I 3042346330 7-062 P.002/007 Flfl `: . Activation of Androgen Response Element by Cadmiam: A Potential Mechanism for a Carcinogenic EffectofCadmium in the Prostate Cadmium bricity in of bath mpational and enviradmentalcozmm~Cadmiumwasdesignated asahamanaw5mgenbythelatgnatiaaalAgemy forResearrchonCanoer(IAILC)in1993.Itisthe d y metalthathasheenrepaatedtobecapable of inducing tumor in the pmatete, which has been d- infinimnl e x p ~ h ~ ~ t 2aL. " proatate c i l ~ hpa~s &~ed increasing atten- tioa in theUnited Stah3 becaarsoit is tbeser-oad leading cause4 of cancer deark24A;Limal studies have ahawn that cadmiumadminiatrat e d b y w io- routes was able to induce proatate caneerin 21. ZE Although induction of proatate cancer by cadmium requires input of tsetieuLaf h e - tion,=. 21 th.e mechanism by which thia metal erauses &Ymstatecancer mImlin* Q be elddated. B e c a w it i s well establiuhed that atoeterone W 2 6 - 2 0 0 1 O1:26an FrorHUPP LIBRARY YEETAL c +I 3042348330 1-062 P.Q03/007 F171 b 2 6 - 2 0 0 1 0 9 : 2 5 a ~ Fron-HUPP LIBRARY > * q-- +I 3042348330 7-062 P.004/007 F-171 In thh stud5 the mdmgen reporGK plaamid wasintroduced iotaLNCap cellsbylipafectamine magent, and responsiveness of the reporwr t o cadmiurn was demdned in the tssnsiont g e ~ t t m n a k t h assay. The remrltr; shaw that cadmium was able to actiPate the reparter activity apdtheactiMtionWaSaseoeiacedwith cadmium concentration ( b e 1). A light indnctian ofthe repmtcradMbetivitywaa observed at 1FrM cadxtium, ~dthhacLiva~~mam`mizedatZb~cad- mium.-winERlllrrimnled to a decrease in the repor&r reepowiveness. Thee8 fll(RJtB demonstratethatin the absenceof admgan, cadmium w88 able EO activate the an- FIGURE2. A b h ofthe androgen reporter drogen responsiverep*. Theretare,it is poasibie that cadmium may chars a biological activity with andmgen. by csdmium in HepG2 celk HepG2 cella we- plated in a Wall culture plate at 1x 106ceWwell 1 day More nmdkuw~Thecells were mnsf e e d a8 stated inthe Mat&aI and M e w see @ CadmiumA c t i u i ~is Dependent on the Amhgetz Reaptor. Theandrogenr#.sptorisatranscrip- ticin. Twenty fm hours 6trand-n, cells we= trea- w i t h 2 plkl mdmium (CdCW. The ceflswereharvestedbr thereporteraesags24hn tion fkta,and its activation is cantmlled by the later Each point represents a mean t SD from 3 avdabilicy of androgenThe above experimental independentexperiments*indicatesa s i d c a n t results demonstrate that cadmium activates the iucreaso fram the conttol (p s 0.05). F&-26-2001 09:26am From-HUPP LIBRARY c dEpT0 2M10, Volume 19,Numher3 Fob-26-2001 00:27aa F r d U P P LIBRARY . .-.*-:, +I 3042348330 r-062 P.OO~/OO? ~-171 F6b-26-2001 09:27an F r d U P P LIBRARY +I 3042348330 T-062 P.007/007 F-171 JEPro 2000,Volume 19,N& 3 TO: m0M: -NE: &pp Weal Lib304-234-8771 -Fax ( 3 0 4 ) 234 8330 .0th Valley Health Services and Education Corpcration 2mo Eoff Streel Whecrling, Wv 2f%m