A simple method for assessment of rat cytochrome P-448 isozymes responsible for the mutagenic activation of carcinogenic chemicals

Mutat Res. 1988 Oct;203(5):333-8. doi: 10.1016/0165-1161(88)90029-5.

Abstract

Cytochrome P-448H/L-enriched and cytochrome P-448L-enriched microsomes were prepared from the livers of Sprague-Dawley rats treated with 3-methylcholanthrene (MC) and with a combination of MC and carbon tetrachloride, respectively, and their activities for mediating mutagenic activation of 9 carcinogenic aromatic amines and benzo[a]pyrene, which are found to be different from cyt. P-450 isozymes as to mutagenic activation, were compared on the basis of microsomal cytochrome P-450 content using Salmonella typhimurium TA98 as a tester bacterium. With regard to the substrate-specificity of cytochrome P-448 isozymes, the present results reflected the reported results with use of a cytochrome P-450-reconstituted system. These findings indicate that the mutation test with cytochrome P-448H/L-enriched and cytochrome P-448L-enriched microsomes could be used as a simple method for the determination of the cytochrome P-448 isozymes responsible for the mutagenic activation of carcinogens and mutagens without the use of a cytochrome P-450-reconstituted system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / metabolism
  • Animals
  • Biotransformation
  • Carbon Tetrachloride / pharmacology
  • Carcinogens / metabolism
  • Carcinogens / pharmacokinetics*
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytochromes / metabolism*
  • Isoenzymes / analysis
  • Methylcholanthrene / pharmacology
  • Microsomes, Liver / enzymology
  • Mutagenicity Tests
  • Phenobarbital / pharmacology
  • Rats

Substances

  • Amines
  • Carcinogens
  • Cytochromes
  • Isoenzymes
  • Methylcholanthrene
  • Cytochrome P-450 Enzyme System
  • Carbon Tetrachloride
  • Cyp1a2 protein, rat
  • Cytochrome P-450 CYP1A2
  • Phenobarbital