Hepa-1 enzyme induction assay as an in vitro indicator of the CYP1A1-inducing potencies of laboratory rodent diets in vivo

Life Sci. 1994;55(24):1945-54. doi: 10.1016/0024-3205(94)00527-3.

Abstract

The Hepa-1 enzyme induction assay (assay of the induction of CYP1A1 catalytic activities in the Hepa-1 mouse hepatoma cell line by various compounds or mixtures) was evaluated as an in vitro indicator of the CYP1A1-inducing potencies of laboratory rodent diets in vivo. C57BL/6J mice were fed for three weeks four selected commercially available diets (one semisynthetic and three standard natural ingredient diets) exhibiting different enzyme-inducing effects in the Hepa-1 assay. beta-Naphthoflavone mixed in a semisynthetic diet (33 and 330 mg/kg of diet) was used as a model inducer. CYP1A1-dependent enzyme activities (aryl hydrocarbon hydroxylase and 7-ethoxyresorufin O-deethylase) were measured in the small intestinal mucosa and liver. There was good agreement between the induction of CYP1A1 in vitro and in vivo: the rank order of the enzyme activities elicited by the diets was the same in the mice as in the Hepa-1 cells. The standard diets were less effective inducers than beta-naphthoflavone in the Hepa-1 cells and in the mice, especially in the small intestinal mucosa. The Hepa-1 enzyme induction assay thus seems to be a mechanistically sound, reliable and sensitive in vitro indicator of the CYP1A1-inducing potencies of laboratory rodent diets in vivo.

MeSH terms

  • Animal Feed* / toxicity
  • Animals
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Benzoflavones / pharmacology
  • Cell Death
  • Cell Line
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Enzyme Induction
  • Food, Formulated
  • Intestinal Mucosa / enzymology*
  • Intestine, Small / drug effects
  • Intestine, Small / enzymology
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidoreductases / biosynthesis
  • Tumor Cells, Cultured
  • beta-Naphthoflavone

Substances

  • Benzoflavones
  • beta-Naphthoflavone
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP1A1