inflammation; inhibit angiogenesis, endothelial cell migration and endothelial cell proliferation; and inhibit the growth and metastasis of human breast and prostate cancer cell lines. It is suggested that the EDP and EEQ metabolites function in humans as they do in animal models and that, as products of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid, the EDP and EEQ metabolites contribute to many of the beneficial effects attributed to dietary omega-3 fatty acids. EDP and EEQ metabolites are short-lived, being inactivated within seconds or minutes of formation by epoxide hydrolases, particularly soluble epoxide hydrolase, and therefore act locally. CYP1A1 is one of the main extra-hepatic cytochrome P450 enzymes; it is not regarded as being a major contributor to forming the cited epoxides but could act locally in certain tissues such as the intestine and in certain cancers to do so. Regulation 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. Additionally, the tumour suppressor p53 has been shown to impact CYP1A1 expression thereby modulating the metabolic activation of several environmental carcinogens such as PAHs. Polymorphisms Several polymorphisms have been identified in CYP1A1, some of which lead to more highly inducible AHH activity. CYP1A1 polymorphisms include: 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. References Further reading 1