PT - JOURNAL ARTICLE AU - J C English AU - M W Anders TI - Evidence for the metabolism of N-nitrosodimethylamine and carbon tetrachloride by a common isozyme of cytochrome P-450. DP - 1985 Jul 01 TA - Drug Metabolism and Disposition PG - 449--452 VI - 13 IP - 4 4099 - http://dmd.aspetjournals.org/content/13/4/449.short 4100 - http://dmd.aspetjournals.org/content/13/4/449.full SO - Drug Metab Dispos1985 Jul 01; 13 AB - Carbon tetrachloride administration to rats produced a selective loss of hepatic cytochrome P-450-dependent catalytic activities. Of the cytochrome P-450-dependent catalytic activities tested, the metabolism of carbon tetrachloride to phosgene and the low Km N-nitrosodimethylamine demethylase were the most sensitive to destruction by carbon tetrachloride. A 50% or greater loss in these catalytic activities was observed 3 hr after giving 10 microliters carbon tetrachloride/kg. Related catalytic activities, such as the microsomal metabolism of carbon tetrachloride to chloroform and the high Km N-nitrosodimethylamine demethylase, were diminished less than 20% 3 hr after giving 10 microliters carbon tetrachloride/kg. To investigate further the relationship between the metabolism of N-nitrosodimethylamine and carbon tetrachloride, the effect of pyrazole, a known inducer of the low Km N-nitrosodimethylamine demethylase, on carbon tetrachloride metabolism was studied. Pyrazole treatment produced a 5.6-fold increase in the microsomal metabolism of carbon tetrachloride to phosgene and a 1.9-fold increase in the conversion of carbon tetrachloride to chloroform. The similarities between both the loss and the induction of the low Km N-nitrosodimethylamine demethylase and the metabolism of carbon tetrachloride to phosgene suggest that these catalytic activities represent a common isozyme of cytochrome P-450. Analysis of cytochromes P-450 by HPLC provided evidence for an isozyme of cytochrome P-450 inducible by pyrazole and destroyed by carbon tetrachloride.