Cell-specific oxidative DNA damage induced by estrogen in rat testicular cells in vitro.
17 alpha-Ethinylestradiol (EE) can induce oxidative DNA damage in terms of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in rat testicular cells by an apparent estrogen receptor-mediated mechanism. We investigated differential susceptibility to EE in cell sub-populations from rat testes and the role of rat 8-oxo-guanine DNA glycosylase (rOGG1). Isolated rat testicular cells were incubated with EE concentrations ranging from 0.1 to 1000 nM. Single strand DNA breaks and oxidised purines as fapyguanine glycosylase (FPG) sensitive sites were assessed by the comet assay. In the total cell population and in round haploid cells, oxidised purines showed a bell-shaped concentration-response relationship with a maximally increased levels at 10 nM EE, whereas, no significant effects were seen in diploid, S-phase or tetraploid cells. The mRNA level of rOGG1 in testes cells was unaffected by EE, whereas, baseline levels were higher than in liver tissue and similar to colon tissue.
Wellejus
Anja
A
Department of Environmental and Occupational Health, The Panum Institute, Institute of Public Health, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. anja.wellejus@farmakol.ku.dk
Bornholdt
Jette
J
Vogel
Ulla B
UB
Risom
Lotte
L
Wiger
Richard
R
Loft
Steffen
S
D000818:Animals; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D043382:DNA-Formamidopyrimidine Glycosylase / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000633:toxicity*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011003:Ploidies; D012333:RNA, Messenger / Q000235:genetics; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D004997:Ethinyl Estradiol; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; D043382:DNA-Formamidopyrimidine Glycosylase