Receptor-mediated ethinylestradiol-induced oxidative DNA damage in rat testicular cells.
Estrogenic chemicals are suspected of affecting cancer risk and male reproduction, possibly involving oxidative DNA damage. In this study, formation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG), was measured in testicular cells from rats after 17 alpha-ethinylestradiol (EE) exposure in vivo and in vitro after incubation with EE with or without an antiestrogen. In vivo, preadult (30-35 days) and adult (110-120 days) Wistar rats received 0, 2.8, or 56 mg EE/kg body weight as intraperitoneal injections (n=6). After 1 or 4 h, the 8-oxodG/10(6) dG ratio was measured in the liver, kidneys, and testes. Testes DNA analysis revealed an age-related effect (adult animals had a higher ratio than the young animals) and a concentration effect in preadult rats (increased EE-concentration caused increased ratio), but no time effect. No differences were found in the liver or kidneys. In vitro, testicular cells were isolated and incubated with EE concentrations ranging from 0.1 to 1000 nM. The results indicated an increase in 8-oxodG/10(6) dG from 0 to 10 nM estrogen. At 1000 nM, the level was close to control level. Coincubation of 10 nM EE (maximum damage) with an estrogen antagonist, ICI 182.780, abolished the effect at 10 nM, indicating that the damaging effect is estrogen receptor mediated.
Wellejus
Anja
A
Institute of Public Health, University of Copenhagen, Denmark.
Loft
Steffen
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000367:Age Factors; D000818:Animals; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D000077267:Fulvestrant; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004997:Ethinyl Estradiol; D004958:Estradiol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione