Metabolism of the hamster pancreatic carcinogen methyl-2-oxopropylnitrosamme by hamster liver and pancreas

Background, The mechanism whereby methyl-2-oxoprspylnitrosamine (MOP) is ac tivated remains unknown, To begin investigating this mechanism, we followed MOP disappearance during its incubation with liver and pancreatic slices a nd homogenates from Syrian hamsters and rats, Methods, after the incubations, disappearance of 100 mu M MOP and appearanc e of a metabolite was followed by high-performance liquid chromatography (H PLC) with ultraviolet (UV) detection, Results, Disappearance rates were 1,2 nmol/mg protein/h for hamster liver s lices; zero for hamster pancreatic slices, ducts and acini; aero for rat li ver and pancreatic slices; and 11.8, 12.8, 1.3, and 2.3 nmol MOP/mg/h for h amster liver homogenate and cytosol, and hamster pancreas homogenate and mi crosomes, respectively, The principal MOP metabolite was identified as meth yl-2-hydroxypropylnitrosamine (MHP) by its HPLC behavior and its H-1-NMR an d mass spectra, MHP yields were generally similar to MOP consumption, but w ere zero for hamster pancreatic homogenate despite its ability to metaboliz e MOB, Conclusion, MOP is a pancreatic carcinogen in hamsters but not in rats, In metabolic studies, hamster liver slices and homogenate (especially the cyto sol) produced MHP from MOP, This is probably an inactivation reaction, Hams ter pancreas homogenate (especially the microsome fraction), but not rat pa ncreas homogenate, metabolized MOP without forming MHP, indicating another route metabolism, perhaps activation to give the proximal carcinogen.