Molecular cloning and functional analysis of cynomolgus monkey CYP1A2

Biochem Pharmacol. 1998 Jul 1;56(1):131-9. doi: 10.1016/s0006-2952(98)00100-2.

Abstract

Complementary DNA fragments encoding cynomolgus monkey CYP1A2 were amplified by the reverse transcriptase-polymerase chain reaction (RT-PCR) method from the liver total RNA of a 3-methylcholanthrene (3-MC)-treated cynomolgus monkey. The nucleotide sequence determined was 1630 bp long and contained an open reading frame for a polypeptide of 516 residues. The nucleotide and the deduced amino acid sequences of cynomolgus monkey CYP1A2 showed 95.1 and 92.8% identities to those of human CYP1A2, respectively. The level of CYP1A2 mRNA in the liver of untreated cynomolgus monkey was very low. Treatment with 3-MC increased it. Still, it was one-fortieth that of CYP1A1. Cynomolgus monkey CYP1A2 expressed in recombinant yeasts activated 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8dimethylimidazo[4,5-flquinoxaline (MeIQx) at efficient rates in the umu mutagenicity test. This cytochrome P450 (CYP) also activated 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), but less efficiently. These results indicate that cynomolgus monkeys have a functionally active CYPIA2 gene, but its expression level is very low in the liver of untreated cynomolgus monkeys.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Cytochrome P-450 CYP1A2 / genetics*
  • Cytochrome P-450 CYP1A2 / metabolism
  • DNA, Complementary
  • Female
  • Humans
  • Liver / enzymology
  • Macaca fascicularis
  • Male
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • DNA, Complementary
  • RNA, Messenger
  • Cytochrome P-450 CYP1A2

Associated data

  • GENBANK/D86474