Molecular cloning and functional analysis of cynomolgus monkey CYP1A2.
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.
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
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T
Sakuma
M
M
Hieda
T
T
Igarashi
S
S
Ohgiya
R
R
Nagata
N
N
Nemoto
T
T
Kamataki
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008252:Macaca fascicularis; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D012333:RNA, Messenger; D019388:Cytochrome P-450 CYP1A2