The inhibition of DNA repair capacity by stilbene estrogen in Leydig cells: its implications in the induction of instability in the testicular genome.
In this study, we examined the effect of stilbene estrogen, diethylstilbestrol (DES), on the DNA repair capacity of mouse Leydig cells using the host cell reactivation assay. Cells transfected with UV-damaged plasmids, undamaged plasmids, or no plasmids (sham treatment) were grown in serum, serum-free, or DES plus serum-free medium. The serum-grown cells which have a shorter cell cycle time (16h) showed a 40% decrease in DNA repair capacity when compared to serum-free cells with a longer cell cycle time (25h). A significant decrease in the DNA repair capacity of the Leydig cells exposed to DES was observed compared to untreated cells grown in a serum-free environment (P<0.05). The effect of DES on DNA repair in Leydig cells was dose dependent. We have recently shown that DES stimulates the growth of Leydig cells. Stimulatory growth of Leydig cells coupled with a decrease in DNA repair capacity by DES may allow the accumulation of mutagenic lesions in DNA. The mutagenic lesions may result from the attack of redox cycling products of DES and/or errors of replication. This, in turn, may produce alterations in the genome of Leydig cells resulting in genetically unstable cells that may serve as precursor cells for testicular carcinogenesis.
DuMond
J W
JW
Department of Environmental Health Sciences, University of Alabama at Birmingham, 317 Ryals Building, 1665 University Blvd., Birmingham, AL 35294-0022, USA.
Roy
D
D
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D004054:Diethylstilbestrol / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D016678:Genome; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D010957:Plasmids / Q000235:genetics; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol; D015500:Chloramphenicol O-Acetyltransferase