Hepa-1 enzyme induction assay as an in vitro indicator of the CYP1A1-inducing potencies of laboratory rodent diets in vivo.
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.
Törrönen
R
R
Department of Physiology, University of Kuopio, Finland.
Kärenlampi
S
S
Pelkonen
K
K
D000821:Animal Feed / Q000633:toxicity; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001571:Benzoflavones / Q000494:pharmacology; D016923:Cell Death; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D005526:Food, Formulated; D007413:Intestinal Mucosa / Q000201:enzymology*; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010088:Oxidoreductases / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1