title: 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.
authors.affiliation: Dept. of Human Exposure Research and Epidemiology, Helmholtz Centre for Environmental Research - UFZ, D-04318 Leipzig, Germany. mario.bauer@ufz.de
authors.forename: Mario
authors.initials: M
authors.lastname: Bauer
authors.forename: Olf
authors.initials: O
authors.lastname: Herbarth
authors.forename: Susanne
authors.initials: S
authors.lastname: Rudzok
authors.forename: Eike
authors.initials: E
authors.lastname: Schmücking
authors.forename: Andrea
authors.initials: A
authors.lastname: Müller
authors.forename: Gabriela
authors.initials: G
authors.lastname: Aust
authors.forename: Carolin
authors.initials: C
authors.lastname: Gräbsch
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000453:epidemiology*; D012333:RNA, Messenger / Q000032:analysis; D012306:Risk; D017423:Sequence Analysis, RNA
chemical_list: D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1