Marmoset CYP1A2: primary structure and constitutive expression in livers.
Complementary DNA of marmoset CYP1A2 was isolated by means of screening the cDNA library and reverse-transcriptase polymerase chain reaction. The deduced amino acid sequence of marmoset CYP1A2 consisted of 516 residues and showed 88.2 and 90.0% identities to corresponding forms in human and cynomolgus monkey, respectively. S1 nuclease protection assay demonstrated that CYP1A2 mRNA was expressed constitutively in the liver, but not in the lung, kidney and small intestine. The level of CYP1A2 mRNA in the liver was increased by treatment with 3-methylcholanthrene and polychlorinated biphenyls. Marmoset CYP1A2 expressed in recombinant yeast activated 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) efficiently, and also activated 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), but at a relatively lower rate in the umu mutagenicity test. Marmoset CYP1A2 also showed ethoxyresorufin O-de-ethylase activity. Based on these results, we demonstrate that marmosets constitutively express CYP1A2 in the liver as in humans.
Sakuma
T
T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Igarashi
T
T
Hieda
M
M
Ohgiya
S
S
Isogai
M
M
Ninomiya
S
S
Nagata
R
R
Nemoto
N
N
Kamataki
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002144:Callithrix; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008252:Macaca fascicularis; D008297:Male; D008969:Molecular Sequence Data; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D015003:Yeasts / Q000201:enzymology
D018076:DNA, Complementary; D012333:RNA, Messenger; D011078:Polychlorinated Biphenyls; D019388:Cytochrome P-450 CYP1A2