Mitogenic signaling mediated by oxidants in retinol treated Sertoli cells.
Recent intervention studies revealed that supplementation with retinoids resulted in a higher incidence of lung cancer. Recently the causal mechanism has begun to be clarified. We report here that retinol-induced oxidative stress is accompanied by cellular proliferation. Retinol (7 microM) significantly induced thiobarbituric acid reactive species (TBARS) formation, which was inhibited by trolox, superoxide dismutase, N-acetylcysteine and ethanol. This was accompanied by an increase in DNA synthesis and focus formation in cultured rat Sertoli cells. Antioxidants and ethanol inhibited retinol-induced DNA synthesis. Our findings suggest that retinol-induced oxidative stress was associated with cellular proliferation complementing our understanding of the significance of retinol supplementation in neoplastic transformation.
Dal-Pizzol
F
F
Departamento de Bioquímica, ICBS-Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. pizzol@ez-poa.com.br
Klamt
F
F
Dalmolin
R J
RJ
Bernard
E A
EA
Moreira
J C
JC
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014801:Vitamin A / Q000494:pharmacology*
D008934:Mitogens; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D014801:Vitamin A; D013936:Thymidine