Cytochrome P450 CYP1A1, induction

Owing to the fact that ethyl ethers are especially effective substrates for CYP1A1 [184], the probe possesses an ethyl group on the phenolic oxygen of the trimethyl lock. In vitro, fluorescence was manifested by CYP1A1 isozyme with Kcat/KM 8.8 x 103 M-1s 1 and KM 0.09 pM. In cellulo, the probe revealed the induction of cytochrome P450 activity by the carcinogen 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD), and its repression by the chemoprotectant resveratrol. 

Dermal treatment of healthy volunteers with 10% coal tar for 4 days produced an 18-fold induction of CYP1A1 mRNA levels in coal-tar-treated skin (Li et al. 1995). In vitro incubation of DNA with coal tar fume concentrates in the presence of mouse and yeast microsomes expressing various cytochrome P450 isoforms or the aryl hydrocarbon hydroxylase receptor (AHR) demonstrated that coal tar fume condensates require metabolic activation to produce DNA adducts (Genevois et al. 1998). Both the AHR and CYP1A were involved in the metabolism of coal tar fume condensate. It was also shown that the reactive metabolites formed by CYP1A are substrates for microsomal epoxide hydrolase. 

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