MUTAGENICITY OF CARCINOGENIC NITROSAMINES WHEN ACTIVATED BY HAMSTER AND HUMAN PANCREATIC DUCT EPITHELIAL-CELLS

We have measured the ability of pancreatic duct epithelial cells (DEC) from Syrian hamsters and humans and CK cells, immortalized hamster DE C, to metabolize chemical carcinogens to species that were mutagenic i n S. typhimurium TA98 and in V79 cells. The chemicals were N-nitrosobi s(2-osopropyl)amine (BOP), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butan one (NNK) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The ability of ethanol (EtOH) to modify the metabolizing efficiency wa s also measured. When an S9 preparation from EtOH-treated CK cells was used to metabolize NNK the number of revertants was 271 +/- 73 compar ed with 17 +/- 2 when the S9 from control CK cells was used. When hams ter DEC were used there was no increase in the mutation frequency for BOP in V79 cells (64 +/- 20 mutants/10(6) survivors per mu mol) when E tOH-DEC were used. However, the mutation frequencies of NNK and PhIP r ose when the EtOH-treated DEC were used from 62 +/- 31 to 198 +/- 28 m utants/10(6) survivors per mu mol for NNK and rom 94 +/- 25 to 166 +/- 25 mutants/10(6) survivors per mu mol for PhIP. A similar result was obtained when human DEC were used, i.e. no change in BOP mutagenicity and a slight increase in PhIP mutagenicity, from 34 +/- 14 +/- to 65 /- 12 mutants/10(6) survivors per mu mol. There were large increases i n the mutagenicity of NNK with each of the three samples of human DEC that were used, from 75 +/- 0 to 213 +/- 38, 75 +/- 13 to 175 +/- 25 a nd 38 +/- 13 to 285 +/- 25 mutants/10(6) survivors per mu mol. The EtO H treatment regimen that was used more closely mimicked chronic exposu re at low concentrations in vivo. These data show that hamster DEC are capable of metabolizing NNK, which is carcinogenic in these cells in vivo. Furthermore, human DEC metabolized NNK as efficiently as hamster DEC. (C) 1997 Elsevier Science Ireland Ltd.