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

Abstract

Oesophageal papillomas were induced in male F344 rats by continuous exposure to N-nitrosomethylbenzylamine (NMBzA) and N-nitrosomethyl(2-methylbutyl)amine 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 NMBzA (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 autoradiography 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 nuclei of the basal layer and of epithelial cells with incipient keratinization. These findings demonstrate that NMBzA and N-nitrosomethylamylamine and probably related methylalkylnitrosamines are effectively bioactivated in premalignant lesions, indicating that during chronic exposure papillomas can acquire additional mutations that are likely to play a major role in tumour progression.

• Authors: O R Dirsch, M Koenigsmann, B I Ludeke, E Scherer, P Kleihues
• Journal: Carcinogenesis (Carcinogenesis) Vol. 11 Issue 9 Pg. 1583-6 (Sep 1990) ISSN: 0143-3334 [Print] England
• PMID: 2401047 (Publication Type: Journal Article)

Chemical References

• Carbon Radioisotopes
• Carcinogens
• Nitrosamines
• N-nitrosomethyl(2-methylbutyl)amine
• N-amyl-N-methylnitrosamine
• nitrosobenzylmethylamine
• O(6)-methyl-2'-deoxyguanosine
• Deoxyguanosine
• Dimethylnitrosamine

Topics

• Animals
• Autoradiography
• Biotransformation
• Carbon Radioisotopes
• Carcinogens (metabolism)
• Deoxyguanosine (analogs & derivatives, analysis)
• Dimethylnitrosamine (metabolism, toxicity)
• Esophageal Neoplasms (chemically induced, metabolism, pathology)
• Male
• Nitrosamines (metabolism, toxicity)
• Papilloma (chemically induced, metabolism, pathology)
• Rats
• Rats, Inbred F344