Human P1-450 gene sequence and correlation of mRNA with genetic differences in benzo[a]pyrene metabolism.

The human P1-450 gene (6,311 base pairs), as well as the 5' (1,604 bases) and 3' (113 bases) flanking regions, have been completely sequenced. Four highly homologous boxes (61, 82, 56 and 97 base pairs) between the human and mouse P1-450 genes are found in the "TATA" box promoter region, -226, -338, and -450 upstream from the cap site, respectively. Nine genomic-DNA samples were digested with each of 23 restriction endonucleases and probed with human P1-450 cDNA fragments; restriction fragment length polymorphisms are detected, although it remains to be seen whether such a recombinant DNA test will be useful in determining individuals at increased risk for cigarette smoking-induced cancer and toxicity. We show in this report, however, that human inducible P1-450 mRNA concentrations are very highly correlated (r = 0.98; N = 6) with genetic differences in benzo[a]pyrene metabolism in mitogen-activated lymphocyte cultures.