PT - JOURNAL ARTICLE AU - D E Rickert AU - S D Held TI - Metabolism of chloronitrobenzenes by isolated rat hepatocytes. DP - 1990 Jan 01 TA - Drug Metabolism and Disposition PG - 5--9 VI - 18 IP - 1 4099 - http://dmd.aspetjournals.org/content/18/1/5.short 4100 - http://dmd.aspetjournals.org/content/18/1/5.full SO - Drug Metab Dispos1990 Jan 01; 18 AB - The metabolism of radiolabeled monochloronitrobenzene isomers was compared in isolated hepatocytes and hepatic subcellular fractions from male Fischer-344 rats. 2-Chloronitrobenezene was converted by isolated hepatocytes to 2-chloroaniline, 2-chloroaniline-N-glucuronide, and S-(2-nitrophenyl)glutathione in approximately equal quantities (13-19% of the added substrate in 90 min). The major metabolite formed from 3-chloronitrobenzene by isolated hepatocytes was 3-chloroaniline (31% of the added substrate in 90 min). Smaller amounts of 3-chloroaniline-N-glucuronide and 3-chloroacetanilide were formed (7 and 17% of the added 3-chloronitrobenzene, respectively, in 90 min). 4-Chloronitrobenzene was metabolized to 4-chloroacetanilide, 4-chloroaniline, and S-(4-nitrophenyl)glutathione in approximately equal amounts (10-15% of the added substrate in 90 min). Studies with hepatic microsomes showed that reduction of the chloronitrobenzenes to chloroanilines was inhibited by SKF 525-A, metyrapone, and carbon monoxide, suggesting that cytochrome P-450 played a role in the reaction. Thus, the major difference in the in vitro hepatic metabolism of the three isomers of chloronitrobenzene is the failure of 3-chloronitrobenzene to be converted to a glutathione conjugate.