MOLECULAR-CLONING AND FUNCTIONAL-ANALYSIS OF CYNOMOLGUS MONKEY CYP1A2

Complementary DNA fragments encoding cynomolgus monkey CYP1A2 were amp lified by the reverse transcriptase-polymerase chain reaction (RT-PCR) method from the liver total RNA of a 3-methylcholanthrene (3-MC)-trea ted cynomolgus monkey. The nucleotide sequence determined was 1630 bp long and contained an open reading frame for a polypeptide of 516 resi dues. The nucleotide and the deduced amino acid sequences of cynomolgu s monkey CYP1A2 showed 95.1 and 92.8% identities to those oi human CYP 1A2, respectively. The level oi CYP1A2 mRNA in the liver oi untreated cynomolgus monkey was very low. Treatment with 3-MC increased it. Stil l, it was one-fortieth that of CYP1A1. Cynomolgus monkey CYP1A2 expres sed in recombinant yeasts activated 2-amino-3-methylimidazo[4,5-f]quin oline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) a t efficient rates in the umu mutagenicity test. This cytochrome P450 ( CYP) also activated 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (P hIP), but less efficiently. These results indicate that cynomolgus mon keys have a functionally active CYP1A2 gene, but its expression level is very low in the liver oi untreated cynomolgus monkeys. BIOCHEM PHAR MACOL 56;1:131-139, 1998. (C) 1998 Elsevier Science Inc.