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