N-Nitrosobis(2-oxopropyl)amine (BOP) and N-nitroso(2-hydroxypropyl)(2-oxypropyl)amine (HPOP) induce pancreatic
tumors in the Syrian hamster. BOP and HPOP target the kidneys, esophagus and upper respiratory system in rats, but the pancreas of this species is resistant to the above
carcinogens. On the other hand,
N-nitrosodimethylamine (DMN) induces hepatic and kidney
tumors in the rat, and
tumors of the liver and upper respiratory system in the hamster, but it is not known to affect the pancreas of either species. At equimolar doses, ratios of DMN versus BOP or HPOP mediated methylation in hamster liver
DNA are 1.6 and 8.1, respectively. Respective ratios in the rat liver are 1.1 and 6.5. However, in both species equitoxic doses of BOP, HPOP and DMN induce similar levels of
N7-methylguanine (N7-MeG) in hepatic
DNA. At such doses methylation of kidney
DNA is 24 and 14 times more extensive in BOP and HPOP than in DMN-treated hamsters. Similarly, ratios of N7-MeG in the pancreas of BOP and HPOP vs. DMN-treated hamsters are 10 and 5, respectively, while in the lung this ratio is 2.2 for both
carcinogens. Levels of
O6-methylguanine (O6-MeG) in the
DNA of extrahepatic tissues are substantially greater in hamsters treated with BOP or HPOP than in those treated with an equitoxic dose of DMN. In rats, equitoxic doses of BOP and DMN induce similar levels of N7-MeG and O6-MeG in hepatic, kidney and lung
DNA. However, levels of these adducts in pancreatic
DNA are 2 times greater following BOP than DMN administration. Ratios of N7-MeG in pancreas, lung and kidney in HPOP vs. DMN-treated rats are 2.1, 2.7 and 2.1, respectively. Repair of O6-MeG is more effective in rat than in hamster liver, however in other tissues this is not always the case. Levels of O6-MeG in the pancreas of rats are reduced to half of their initial value between 40 and 50 h following the administration of 10, 50 or 20 mg/kg DMN, HPOP or BOP, respectively. However, half-lives for the repair of O6-MeG in hamster pancreas are 28, 62 and greater than 120 h at the respective doses of the above
carcinogens. Since the above doses of DMN, HPOP and BOP induce 7, 19 and 41 nmol O6-MeG/mmol of
guanine respectively in the hamster pancreas, it is suggested that the rate of repair could be a function of the initial concentration of this adduct. Differences between DMN and BOP or HPOP in methylating pancreatic
DNA are sufficient to distinguish the latter two
nitrosamines as pancreatic
carcinogens for the hamster.