Cloning and isolation of human cytochrome P-450 cDNAs homologous to dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6

DNA. 1985 Oct;4(5):395-400. doi: 10.1089/dna.1985.4.395.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Cytochrome P-450 Enzyme System / genetics*
  • DNA / genetics
  • DNA Restriction Enzymes
  • Dioxins / pharmacology
  • Enzyme Induction / drug effects
  • Humans
  • Mice
  • Rabbits

Substances

  • Dioxins
  • DNA
  • Cytochrome P-450 Enzyme System
  • DNA Restriction Enzymes

Associated data

  • GENBANK/M12078
  • GENBANK/M12079