RT Journal Article
SR Electronic
T1 Metabolism of chloronitrobenzenes by isolated rat hepatocytes.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 5
OP 9
VO 18
IS 1
A1 D E Rickert
A1 S D Held
YR 1990
UL http://dmd.aspetjournals.org/content/18/1/5.abstract
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.