EVIDENCE FOR THE METABOLISM OF N-NITROSODIMETHYLAMINE AND CARBON-TETRACHLORIDE BY A COMMON ISOZYME OF CYTOCHROME-P-450

  • 1 January 1985
    • journal article
    • research article
    • Vol. 13  (4) , 449-452
Abstract
CCl4 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 CCl4 to phosgene and the low Km N-nitrosodimethylamine demethylase were the most sensitive to destruction by CCl4. A 50% or greater loss in these catalytic activities was observed 3 h after giving 10 .mu.l CCl4/kg. Related catalytic activities, such as the microsomal metabolism of CCl4 to chloroform and the high Km N-nitrosodimethylamine demethylase, were diminished < 20% 3 h after giving 10 .mu.l CCl4/kg. To investigate further the relationship between the metabolism of N-nitrosodimethylamine and CCl4, the effect of pyrazole, a known inducer of the low Km N-nitrosodimethylamine demethylase, on CCl4 metabolism was studied. Pyrazole treatment produced a 5.6-fold increase in the microsomal metabolism of CCl4 to phosgene and a 1.9-fold increase in the conversion of CCl4 to chloroform. The similarities between both the loss and the induction of the low Km N-nitrosodimethylamine demethylase and the metabolism of CCl4 to phosgene suggest that these catalytic activities represent a common isozyme of cytochrome P-450. Analysis of cytochromes P-450 by HPLC [high-performance liquid chromatography] provided evidence for an isozyme of cytochrome P-450 inducible by pyrazole and destroyed by CCl4.