Bioactivation of N-nitrosomethylbenzylamine and N-nitrosomethyl-amylamine in oesophageal papillomas.
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.
Dirsch
O R
OR
Institute of Pathology, University of Zürich, Switzerland.
Koenigsmann
M
M
Ludeke
B I
BI
Scherer
E
E
Kleihues
P
P
D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004128:Dimethylnitrosamine / Q000378:metabolism / Q000633:toxicity / Q000031:analogs & derivatives; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009602:Nitrosamines / Q000378:metabolism* / Q000633:toxicity; D010212:Papilloma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D002250:Carbon Radioisotopes; D002273:Carcinogens; D009602:Nitrosamines; C065838:N-nitrosomethyl(2-methylbutyl)amine; C025033:N-amyl-N-methylnitrosamine; C014707:nitrosobenzylmethylamine; C015558:O(6)-methyl-2'-deoxyguanosine; D003849:Deoxyguanosine; D004128:Dimethylnitrosamine