The metabolism of the pancreas carcinogen N-nitrosobis(2-oxopropyl)amine by hamster pancreas duct epithelial cell clones; evidence for different metabolic efficiencies and response to cytochrome P450 inducers.

CONTEXT We have isolated five stable clones from a primary culture of Syrian golden hamster pancreatic duct epithelial cells and have designated them as CK1 through CK5. DESIGN Here we describe the ability of two of these, CK1 and CK5, to metabolize the pancreas carcinogen N-nitrosobis(2-oxopropyl)amine. The metabolism was assessed as the production of mutated V79 cells in a CK cell/V79 co-culture set up. RESULTS At a dose of 0.1 mM N-nitrosobis(2-oxopropyl)amine, the CK1 cells produced 82.3 +/- 17.2 mutants/1,000,000 survivors while the CK5 cells produced only 33.2 +/- 10.8 mutants/1,000,000 survivors, both are mean +/- SD (n = 8). Furthermore, both cell types responded differently to two inducers of cytochrome P450 activity, namely Arochlor 1254 and EtOH. Arochlor 1254 treatment did not affect the metabolizing ability of CK1 cells while EtOH treatment resulted in a twofold increase in the mutation frequency. Arochlor and EtOH treatment inhibited the ability of CK5 cells to metabolize N-nitrosobis(2-oxopropyl)amine. CONCLUSIONS These data show that the duct epithelium of the pancreas is a multi-cellular tissue and the different cell types within the epithelium have different abilities to metabolize xenobiotic chemicals.