Stable expression of human cytochrome P450IA2 cDNA in a human lymphoblastoid cell line: role of the enzyme in the metabolic activation of aflatoxin B1

Mol Carcinog. 1990;3(1):5-8. doi: 10.1002/mc.2940030104.

Abstract

A human lymphoblastoid cell line stably expressing a human cytochrome P450IA2 cDNA was developed. This recombinant cell line displayed P450IA2 protein and estradiol 2-hydroxylase activity, neither of which was detected in the parental cell line. The recombinant cell line was also approximately 1000-fold more sensitive to the cytotoxicity and mutagenicity of the carcinogenic mycotoxin aflatoxin B1 than was the parent cell line. The increase in mutagenicity was supported by a corresponding increase in the level of aflatoxin B1 binding to DNA in cells expressing P450IA2 relative to control cells.

MeSH terms

  • Aflatoxin B1
  • Aflatoxins / metabolism*
  • Aflatoxins / toxicity
  • B-Lymphocytes
  • Biotransformation
  • Blotting, Western
  • Cell Division / drug effects
  • Cell Line
  • Cytochrome P-450 CYP1A1*
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • DNA / biosynthesis
  • DNA / genetics
  • DNA / metabolism*
  • Gene Expression*
  • Humans
  • Mutagens
  • Steroid Hydroxylases / metabolism
  • Transfection

Substances

  • Aflatoxins
  • Mutagens
  • DNA
  • Cytochrome P-450 Enzyme System
  • Aflatoxin B1
  • Steroid Hydroxylases
  • Cytochrome P-450 CYP1A1
  • estrogen 2-hydroxylase