METABOLISM OF N-NITROSOMETHYLBENZYLAMINE BY MICROSOMES FROM PERIVENOUS AND PERIPORTAL HEPATOCYTES

Immunohistochemical studies have shown the presence of O-6-methylguani ne in the perivenous area but not the periportal area of the liver lob ule following administration of N-nitrosomethylbenzylamine (NMBzA) to rats. This study was designed to investigate the hypothesis that hepat ic heterogeneity of NMBzA metabolism determines the distribution of O- 6-methylguanine in the liver. Using microsomes prepared from purified perivenous and periportal hepatocytes, we showed that NMBzA debenzylas e and demethylase activities were 2-fold and 1.5-fold higher, respecti vely, 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 O-6-methylguanine in perivenous than in periportal hepat ocytes could explain the localization of this base in zone 3 of the li ver lobule following NMBzA treatment.