Binding of N-nitroso carcinogens in pancreatic tissue

Carcinoma of the pancreas can be produced in guinea pigs by the oral administration of 1-methyl-1-nitrosourea (MNU). Our present studies have examined the distribution of this compound in these animals following parenteral and oral administration and also its specific sites of binding within the pancreatic cell. Emphasis has been placed upon the comparison of the uptake and binding of MNU with the related compound 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), which does not seem to be carcinogenic to the pancreas after oral administration. The distribution data indicate uptake into pancreas that is comparable to that of other organs. Binding data show both MNU and MNNG to extensively modify subcellular organelles and the DNA and proteins of chromatin, but that MNU does this to a somewhat greater extent than MNNG.