Effects of Teratogenic Drugs on CYP1A1 Activity in Differentiating Rat Embryo Cells

Drug Res (Stuttg). 2015 May;65(5):238-43. doi: 10.1055/s-0034-1370966. Epub 2014 Mar 25.

Abstract

CYP1A1, a P450 isoenzyme, is involved in the phase I xenobiotic metabolism including teratogen drugs. In the present study, the ability of teratogens to elevate the embryonic expression of CYP1A1 was examined. Micromass cell cultures prepared from day 13 rat embryo limb buds (LB). LB cells were cultivated and exposed for 5 days to retinoic acid (RA), hydrocortisone (HC), caffeine (CA) and quinine (QN). CYP1A1 protein expression and activity were measured using immunofluorescence staining and ethoxyresorufin O-deethylation (EROD) assay, respectively. The EROD activity increased significantly following LB cells exposure to RA and HC (p<0.05) but the expression of CYP1A1 protein was reduced by these drugs, whereas the expression of CYP1A1 protein and EROD activity decreased significantly following the addition of CA and QN (p<0.05, p<0.01). Our findings show that studied teratogens have potency to increase CYP1A1 activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Cell Differentiation*
  • Cells, Cultured
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / metabolism
  • Hydrocortisone / pharmacology
  • Limb Buds / cytology
  • Quinine / pharmacology
  • Rats
  • Teratogens / pharmacology*
  • Tretinoin / pharmacology

Substances

  • Teratogens
  • Caffeine
  • Tretinoin
  • Quinine
  • Cytochrome P-450 CYP1A1
  • Hydrocortisone