Oxidation at carbon via cytochrome P450 CYP1B1

CYP1B1 has minimal sequence homology with other known members of the CYP1 family. The human CYP1B1 subfamily contains only a single gene, which is located on chromosome 2, contains three exons and codes for the longest known P450 protein at 543 amino acids. CYP1B1 is highly inducible in animals and cell lines by TCDD, DMBA and other polycyclic aromatic hydrocarbons and is induced in human bronchial epithelial cells by cigarette smoking. The dose-response and mechanism of induction appear to be different for CYP1B1 than for CYP1A1 and CYP1A2, with CYP1B1 induction involving both Ah-receptor mediated transcriptional activation and protein stabilization, apparently by the inducing agent. In humans, although low levels of CYP1B1 mRNA may be present in normal cells, CYP1B1 protein appears to be expressed only in cancer cells. CYP1B1 hydroxylates polycyclic aromatic hydrocarbons (PAH) and metabolically activates both PAH and heterocyclic amine procarcinogens. It is active in several "probe" drug metabolism reactions characteristic of human CYP1A1, CYP1A2 and CYP2D6, but inactive in assays more characteristic of other human P450 subfamilies. CYP1B1 is a high affinity oestradiol 4-hydroxylase. One of the major impacts of CYP1B1 on human health may be to facilitate the origination and development of cancer through the formation of 4-hydroxyoestrogens in situ. A genetic deficiency in CYP1B1 is also a principal cause of primary congenital glaucoma.