Molecular cloning and functional expression of a mouse cytochrome P-450 (Cyp3a-13): examination of Cyp3a-13 enzyme to activate aflatoxin B1 (AFB1)

Biochim Biophys Acta. 1994 Dec 15;1201(3):405-10. doi: 10.1016/0304-4165(94)90069-8.

Abstract

A cDNA encoding a novel member of the cytochrome P-450 superfamily, Cyp3a-13, has been isolated from mouse liver cDNA library by hybridization screening. The Cyp3a-13 encoded 503 amino acid residues and shared 71% amino acid identity with Cyp3a-11. When Cyp3a-13 cDNA was expressed in CR119 cells which had been established as a cell line stably expressing NADPH-cytochrome P-450 reductase cDNA of guinea pigs, aflatoxin B1-dependent cytotoxicity was observed. This cytotoxicity was enhanced by alpha-naphthoflavone (7,8-benzoflavone), which is known to augment the CYP3A enzymatic activity. The results indicate that CYP3A in mice, which are relatively insensitive to aflatoxin B1, can activate aflatoxin B1 to a genotoxic product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aflatoxin B1 / metabolism*
  • Aflatoxin B1 / toxicity
  • Animals
  • Benzoflavones / pharmacology
  • Cell Line / enzymology
  • Cloning, Molecular
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • DNA, Complementary / chemistry
  • Guinea Pigs
  • Male
  • Membrane Proteins
  • Mice
  • Molecular Sequence Data
  • NADPH-Ferrihemoprotein Reductase / metabolism

Substances

  • Benzoflavones
  • DNA, Complementary
  • Membrane Proteins
  • alpha-naphthoflavone
  • Cytochrome P-450 Enzyme System
  • Aflatoxin B1
  • Cyp3a13 protein, mouse
  • Cytochrome P-450 CYP3A
  • NADPH-Ferrihemoprotein Reductase

Associated data

  • GENBANK/X63023