The CYP2A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis.
The CYP2A subfamily has been characterized in several mammalian species including mouse, rat, rabbit, hamster, cattle and human. Marked species differences have been demonstrated in the catalytic activities and regulation of this subfamily. In humans, the CYP2A genes are found as a cluster on the long arm of chromosome 19 with the CYP2B and CYP2F genes. Marked interindividual differences in expression of the CYP2A6 gene was found in livers analyzed in vitro and in humans phenotyped in vivo by using coumarin, a specific substrate for the enzyme. Efforts are underway to determine the existence of mutant and variant CYP2A6 alleles in the human population. Since CYP2A6 is able to metabolically-activate chemical carcinogens and is expressed in extrahepatic tissue, it will be of interest to determine whether genetic differences in expression of the gene is associated with cancer risk.
Fernandez-Salguero
P
P
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Gonzalez
F J
FJ
D000818:Animals; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity*; D002417:Cattle; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003374:Coumarins / Q000378:metabolism; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008099:Liver / Q000201:enzymology; D051379:Mice; D005810:Multigene Family; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity
D002273:Carcinogens; D003374:Coumarins; D003577:Cytochrome P-450 Enzyme System; C030123:coumarin; D013250:Steroid Hydroxylases; C022657:steroid hormone 6-beta-hydroxylase