Induction of N-nitrosodimethylamine metabolism in liver and lung by in vivo pyridine treatments of rabbits

N-Nitrosodimethylamine is a procarcinogen that is activated by cytochrome P 450 dependent N-nitrosodimethylamine N-demethylase to labile alpha-carbon h ydroxylated products further resulting in active methylating agents. In viv o intraperitoneal administration of pyridine to rabbits significantly incre ased N-nitrosodimethylamine N-demethylase activity by 6.9- and 5.2-fold in liver and lung microsomes, respectively. Although, p-nitrophenol hydroxylas e and aniline 4-hydroxylase activities were markedly enhanced by pyridine t reatment in liver about 4.4- and 5.8-fold, respectively, no change was obse rved in the activities of these enzymes in lung microsomes. Pyridine treatm ent also elevated P450 contents of liver and lung by 2.04- and 1.4-fold, re spectively. SDS-PAGE of pyridine-induced liver microsomes revealed a protei n band of enhanced intensity having M-r of 51,000 migrating in the region o f cytochrome P4502E1. The results obtained in this study demonstrated for t he first time, a significant 5.2-fold induction of NDMA N-demethylase activ ity in the rabbit lung over the controls. Pyridine is readily absorbed by i nhalation and is a constituent of tobacco and tobacco smoke. Thus induction of NDMA N-demethylase suggests that in the lung, as in the liver, pyridine may stimulate the metabolic activation of this nitrosamine significantly.