Diversity of common alternative splicing variants of human Cytochrome P450 1A1 and their association to carcinogenesis

Abstract

Cytochrome P450 1A1 (CYP1A1) belongs to the enzymes of biotransformation of phase I. CYP1A1 performs the catalytic activation of exogenous and endogenous substrates to more carcinogenic metabolites. Overexpression of the wild-type and a recently described splice variant (CYP1A1v, ovarian cancer) are attributed to neoplastic transformation. Here we describe novel CYP1A1 splicing variants commonly and frequently transcribed in leucocytes of healthy volunteers, separated from variants exclusively expressed in tumour cell lines. Interestingly, all the novel splicing variants in leukocytes are generated by employing of two nested splice site pairs, one outer canonical and one inner non-canonical splice site pair, within the exon 2 of the human CYP1A1. In general, the frequent presence of common splicing variants in healthy volunteers has to be consider as a physiological feature of human CYP1A1 transcription process, rather than a signature of carcinogenesis.