|Cytochrome P450, family 1, subfamily A, polypeptide 1|
|RNA expression pattern|
CYP1A1 is also known as AHH (aryl hydrocarbon hydroxylase). It is involved in the metabolic activation of aromatic hydrocarbons (polycyclic aromatic hydrocarbons, PAH), for example, benzo(a)pyrene (BP), by transforming it to an epoxide. In this reaction, the oxidation of benzo[a]pyrene is catalysed by CYP1A1 to form BP-7,8-epoxide, which can be further oxidized by epoxide hydrolase (EH) to form BP-7,8-dihydrodiol. Finally CYP1A1 catalyses this intermediate to form BP-7,8-dihydrodiol-9,10-epoxide, which is the ultimate carcinogen.
However, an in vivo experiment with gene-deficient mice has found that the hydroxylation of benzo(a)pyrene by CYP1A1 can have an overall protective effect on the DNA, rather than contributing to potentially carcinogenic DNA modifications. This effect is likely due to the fact that CYP1A1 is highly active in the intestinal mucosa, and thus inhibits infiltration of ingested benzo(a)pyrene carcinogen into the systemic circulation.
The expression of the CYP1A1 gene, along with that of CYP1A2/1B1 genes, is regulated by a heterodimeric transcription factor that consist of the aryl hydrocarbon receptor, a ligand activated transcription factor, and the aryl hydrocarbon receptor nuclear translocator. In the intestine, but not the liver, CYP1A1 expression moreover depends on TOLL-like receptor 2 (TLR2), which recognizes bacterial surface structures such as lipoteichoic acid.
- M1, T→C substitution at nucleotide 3801 in the 3'-non-coding region
- M2, A→G substitution at nucleotide 2455 leading to an amino acid change of isoleucine to valine at codon 462
- M3, T→C substitution at nucleotide 3205 in the 3'-non-coding region
- M4, C→A substitution at nucleotide 2453 leading to an amino acid change of threonine to asparagine at codon 461
The highly inducible forms of CYP1A1 are associated with an increased risk of lung cancer in smokers. (Reference = Kellerman et al., New Eng J Med 1973:289;934-937) Light smokers with the susceptible genotype CYP1A1 have a sevenfold higher risk of developing lung cancer compared to light smokers with the normal genotype.