Metabolism of N-nitrosomethylbenzylamine by microsomes from perivenous and periportal hepatocytes.
Immunohistochemical studies have shown the presence of O6-methylguanine in the perivenous area but not the periportal area of the liver lobule following administration of N-nitrosomethylbenzylamine (NMBzA) to rats. This study was designed to investigate the hypothesis that hepatic heterogeneity of NMBzA metabolism determines the distribution of O6-methylguanine in the liver. Using microsomes prepared from purified perivenous and periportal hepatocytes, we showed that NMBzA debenzylase and demethylase activities were 2-fold and 1.5-fold higher, respectively, in perivenous than in periportal microsomes. Our results suggest that the combined effect of a higher rate of formation and lower rate of repair of O6-methylguanine in perivenous than in periportal hepatocytes could explain the localization of this base in zone 3 of the liver lobule following NMBzA treatment.
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Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Canada.
Archer
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D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D002273:Carcinogens; D006147:Guanine; D003577:Cytochrome P-450 Enzyme System; C014707:nitrosobenzylmethylamine; C008449:O-(6)-methylguanine; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D005723:gamma-Glutamyltransferase; D004128:Dimethylnitrosamine