Bioactivation of N-nitrosomethylbenzylamine and N-nitrosomethyl-amylamine in oesophageal papillomas

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Abstract
Oesophageal papillomas were induced in male F344 rats by continuous exposure to N-nitrosomethylbeazylamine (NMBZA) and N-nitrosomethyl(2-methylbutyl)ainine in the drinking water at concentrations of 10 and 19.5 p.p.m. respectively. After 81–141 days animals received a single i.p. chasing dose of NMIBZA (0.1 mmol/kg), [14C-methyl]NMBZA or N-nitroso[14C-methyl]amylamine and were killed 6 h later. Induced papillomas (3–9 per animal) were analysed by autoradlography and by immunohistochemistry using a polyclonal antibody to O6-methyldeoxyguanosine Both techniques revealed the presence of high levels of alkylation products in all papillomas investigated. Immunohistochemical staining of O6-methyldeoxyguanosine was largely restricted to nudei of the basal layer and of epithelial cells with incipient keratinization. These findings demonstrate that NMBZA and N-nitrosomethylamylamine and probably related methyl alkylnitrosamines are effectively bioactivated in premalignant lesions, indicating that during chronic exposure papifiomas can acquire additional mutations that are likely to play a major role in tumour progression.