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/10⁶ 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/10⁶ 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.