title: Role of metabolism and DNA adduct formation in the induction of sister chromatid exchanges in human lymphocytes by diethylstilbestrol.
abstract: Recent studies have shown that diethylstilbestrol (DES) induces sister chromatid exchanges (SCEs) in lymphocytes from pregnant and premenopausal women but has only a slight effect on lymphocytes from post-menopausal women or men. In this study blood specimens from premenopausal women were used to define the role of different metabolic pathways on DES-induced formation of SCEs and to determine whether conditions resulting in induction of SCEs also induced detectable levels of DNA adducts. Exposure of lymphocytes in vitro to 0-40 microM DES induced a concentration-dependent increase in SCEs. Addition of indomethacin to the cultures partially abolished DES-induced SCEs, suggesting involvement of prostaglandin synthetases in the formation of specific DES metabolites that cause SCEs. alpha-Naphthoflavone, an inhibitor of cytochrome P-450 monooxygenases, had no effect on DES-induced SCEs. Cells exposed to DES at doses sufficient to cause large increases in SCE induction did not have adducts detectable by a 32P-postlabeling assay capable of revealing adducts at a level of 1 adduct/10(9) normal nucleotides.
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors.forename: K
authors.initials: K
authors.lastname: Lundgren
authors.forename: K
authors.initials: K
authors.lastname: Randerath
authors.forename: R B
authors.initials: RB
authors.lastname: Everson
mesh_terms: D001571:Benzoflavones / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D012854:Sister Chromatid Exchange / Q000187:drug effects*
chemical_list: D001571:Benzoflavones; C011512:alpha-naphthoflavone; D004054:Diethylstilbestrol; D004247:DNA; D007213:Indomethacin