Cerium-induced strain-dependent increase in Cyp2a-4/5 (cytochrome P4502a-4/5) expression in the liver and kidneys of inbred mice

Biochem Pharmacol. 1992 Oct 6;44(7):1269-74. doi: 10.1016/0006-2952(92)90525-n.


The murine Cyp2a-4 and Cyp2a-5 genes encode P450 isoforms catalysing testosterone 15 alpha-hydroxylase and coumarin 7-hydroxylase (COH) activities, respectively. Two days after the administration of a hepatotoxic dose of cerium chloride (2 mg/kg i.v.), COH activity was increased 3.2-fold in the liver of DBA/2 mice. Three and 4 days after the cerium treatment, coinciding with the occurrence of overt liver damage, there was a dramatic decrease in COH activity. The activities of testosterone 15 alpha-hydroxylase and the Cyp1a-1-mediated 7-ethoxyresorufin O-deethylase (EROD) were decreased in response to cerium. Much less pronounced changes in the enzyme activities occurred in the C57BL/6 mouse liver. Northern blot analysis showed a 21-fold increase in the hepatic Cyp2a-4/5 mRNA in the DBA/2 mice at day 2, whereas no increase occurred in the C57BL/6 mice. Also in the kidneys the increase in COH activity and in Cyp2a-4/5 mRNA was marked only in the DBA/2 mice. A polymerase chain reaction-mediated analysis method utilizing a unique PstI restriction site in the Cyp2a-5 cDNA was used to differentiate between the highly homologous Cyp2a-4 and Cyp2a-5 mRNAs. Cerium was found to increase the amount of hepatic and renal Cyp2a-4 and Cyp2a-5 mRNA only in the DBA/2 mice. These data indicate that the Cyp2a-4/5 complex is regulated in a different way in DBA/2 and C57BL/6 mice and that some association exists between the development of liver damage and COH induction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Base Sequence
  • Blotting, Northern
  • Cerium / toxicity*
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Enzyme Induction / drug effects
  • Gene Expression Regulation / drug effects
  • Kidney / drug effects*
  • Kidney / enzymology
  • Liver / drug effects*
  • Liver / enzymology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mixed Function Oxygenases / biosynthesis
  • Molecular Sequence Data
  • Oxidoreductases / biosynthesis
  • RNA, Messenger / analysis
  • Steroid Hydroxylases / biosynthesis*


  • RNA, Messenger
  • Cerium
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Oxidoreductases
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2A6
  • steroid 15-alpha-hydroxylase
  • cerous chloride