Mutation of V79 cells by N-dialkylnitrosamines after activation by hamster pancreas duct cells.
Pancreas duct epithelial cells (DEC), isolated from hamsters and cultured for up to 25 days, were able to metabolize N-nitrosobis(2-oxopropyl)amine (BOP) to species that were mutagenic in V79 cells. There was no decline in the nitrosamine-activating ability of DEC over the period of observation (25 d). DEC activated N-nitrosobis(2-hydroxypropyl)amine (BHP), N-nitrosodiethylamine (DEN), N-nitrosodimethylamine (DMN) and N-nitrosomethyl(2-oxopropyl)amine (MOP) and BOP in the same assay, although the mutation frequencies for BHP, DEN and DMN were barely different from that for the controls (4 +/- 1 mutants/10(6) cells). The mutation frequencies for a dose of 0.1 mM were BHP, 2 +/- 1; BOP, 113 +/- 7; DEN, 8 +/- 1; DMN, 5 +/- 2; and MOP, 18 +/- 3 (mutants/10(6) cells; means +/- SE). When hepatocytes were used the mutation frequencies were BHP, 3 +/- 1; BOP, 60 +/- 3; DEN, 8 +/- 2; DMN, 8 +/- 2; and MOP, 121 +/- 10. BOP was toxic to the DEC at doses above 0.1 mM. Experiments in which co-factors were omitted from the medium suggested that an isoform(s) of the cytochrome P-450 IIIA family was involved, directly or indirectly, in BOP activation.
Lawson
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Eppley Institute for Research on Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
Kolar
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D000704:Analysis of Variance; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D004052:Diethylnitrosamine / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000633:toxicity; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity*; D009602:Nitrosamines / Q000493:pharmacokinetics / Q000633:toxicity*; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism*
D003470:Culture Media; D009153:Mutagens; D009602:Nitrosamines; D004052:Diethylnitrosamine; C012457:diisopropanolnitrosamine; C028133:N-nitrosomethyl-2-oxopropylamine; C013622:nitrosobis(2-oxopropyl)amine; D003907:Dexamethasone; D004128:Dimethylnitrosamine