Pancreatic carcinogenic nitrosamines in Syrian hamsters

Pancreatic neoplasms similar to those seen in humans have been induced by a group of related nitrosamines only in Syrian golden hamsters. Studies indicate a relationship between the structure of the carcinogens and their affinity for the pancreas: the presence of one keto or hydroxy group in the beta-position on one of the aliphatic chains of alkyl nitrosamines is a prerequisite for their pancreatic carcinogenicity; addition of a second beta-keto group significantly increases their activity on and specificity for the pancreas; replacement of one 2-oxo chain with a methyl group diminishes their specificity for the pancreas as does prolongation of the aliphatic chain. Carboxylation at the 3-position is associated with a complete loss of pancreatotropism. N-Nitrosomethyl(2-oxopropyl)amine appears to be a proximate carcinogenic metabolite of these compounds. The lack of tumour induction in the pancreas of rats correlates with the inability of this species to metabolize carcinogens to this metabolite, whereas all the pancreatic cells of the hamster (ductal/ductular, acinar and islet cells) have this ability. The results of in-vivo and in-vitro studies strongly suggest that the hamster pancreatic ductal and ductular cells are the most active unit of the organ in metabolizing the carcinogen and are also the progenitor cells of the induced pancreatic lesions.