Effects of benzo(a)pyrene and tetrachlorodibenzo(p)dioxin on fetal dolphin kidney cells: inhibition of proliferation and initiation of DNA damage.
Dolphin kidney cells (CDK) were exposed in vitro to benzo(a)pyrene (BaP) in the presence or absence of 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD), a cytochrome P450-inducing agent, and/or alpha-naphthoflavone (alpha NF), an inhibitor of cytochrome P450 induction. BaP inhibited mitosis in CDK cells in a dose-dependent manner. TCDD, while inhibiting cell proliferation, did not show a strict dose-dependent mode of action. BaP inhibition of mitosis was decreased by alpha NF, which also decreased the inhibitory effects of TCDD on CDK proliferation. BaP treatment initiated both 3H-thymidine incorporation and the increased alkali lability of DNA functions of the initiation of excision repair. Cells pre-treated with TCDD and then exposed to BaP exhibited increased BaP-DNA adduct levels and increased DNA excision repair. These data indicate that dolphin cells metabolized BaP in vitro as a function of cytochrome P450-associated activities, that BaP metabolites covalently bound to cellular DNA and initiated excision repair. Inhibition of the cytochrome P450-mediated metabolism of BaP decreased the BaP-associated inhibition of mitosis in dolphin cells.
Carvan
M J
MJ
Department of Anatomy and Public Health, College of Veterinary Medicine, Texas A & M University, College Station 77843.
Flood
L P
LP
Campbell
B D
BD
Busbee
D L
DL
D000818:Animals; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D018736:DNA Adducts / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004289:Dolphins; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001571:Benzoflavones; D018736:DNA Adducts; D000072317:Polychlorinated Dibenzodioxins; D001564:Benzo(a)pyrene; C011512:alpha-naphthoflavone