Cloning and isolation of human cytochrome P-450 cDNAs homologous to dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6.
Human cytochrome P-450s structurally related to 2,3,7,8-tetrachloro-p-dioxin (TCDD)-inducible rabbit P-450 4 and 6 have been cloned from a human liver cDNA library. The human P-450 4 cDNA clone, hpP-450 4, and the human P-450 6 cDNA clone, hpP-450 6, were identified by hybridization to rabbit P-450 4 and P-450 6 cDNAs, respectively. DNA sequence analysis demonstrates that hpP-450 4 is 83% and 75% homologous to rabbit P-450 4 and P-450 6 mRNAs, respectively, whereas hpP-450 6 is 79% and 72% homologous to rabbit P-450 6 and P-450 4, respectively. A comparison of DNA sequence of the two human cDNA clones shows they are 80% homologous. This is similar to the homology found between the cDNA sequences of rabbit P-450 4 and P-450 6. Northern blot analysis has shown that the human P-450 4 mRNA is approximately 3000 bases, while the human P-450 6 mRNA is 2600 bases in length. Clone hpP-450 4 preferentially hybridizes to TCDD-inducible rabbit P-450 4 and mouse P3-450 mRNAs, whereas hpP-450 6 preferentially hybridizes to TCDD-inducible rabbit P-450 6 and mouse P1-450 mRNAs. Both hpP-450 4 and hpP-450 6 recognize different genomic fragments, indicating that each is encoded by different genes. These results indicate the existence of at least two P-450 genes in humans that are highly homologous to the TCDD-inducible P-450s in rabbits and mice.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D004147:Dioxins / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D051379:Mice; D011817:Rabbits
D004147:Dioxins; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D004262:DNA Restriction Enzymes