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.