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


Dirsch, O R; Koenigsmann, M; Ludeke, B I; Scherer, E; Kleihues, P (1990). Bioactivation of N-nitrosomethylbenzylamine and N-nitrosomethyl-amylamine in oesophageal papillomas. Carcinogenesis, 11(9):1583-1586.

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

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

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 January 1990
Deposited On:16 Oct 2018 15:43
Last Modified:24 Nov 2018 03:03
Publisher:Oxford University Press
ISSN:0143-3334
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/carcin/11.9.1583
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093carcin1191583 (Library Catalogue)

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