Positive Correlation Between Pancreatic DNA Damage and Species Specificity in Response to N-Nitrosobis(2-oxopropyl)amine234

Abstract

N-nitrosobis(2-oxopropyl)amine (BOP), a potent pancreatic carcinogen in hamsters that has failed to induce pancreatic tumors in rats, was studied for its effects on the DNA of both rat and hamster pancreas in order to relate DNA damage (as measured by alkaline elution) to carcinogenicity in vivo. At doses of 10, 20, and 40 mg BOP/kg, extensive DNA damage was detected in male Syrian golden hamster pancreas but Lewis rat pancreatic DNA was not affected. Only at doses of 100 mg BOP/kg or greater could pancreatic DNA damage in the rat be detected. DNA damage was also observed in both rat and hamster livers at 10, 20, and 40 mg BOP/kg. Alkaline elution analysis of DNA from isolated rat and hamster acinar cells treated in vitro with BOP revealed that only hamster acinar cell DNA was damaged. Rat acinar cell DNA was unaffected at all doses examined, up to 200 micrograms BOP/ml medium. Unscheduled DNA synthesis studies in cultured acinar cells confirmed the observations that BOP is genotoxic to hamster but not to rat acinar cells. The results strongly suggested that rat pancreas did not have the ability to metabolically activate BOP, which accounted for lack of both BOP-induced DNA damage and carcinogenicity in the rat.