Molecular cloning and expression of novel alternatively spliced cytochrome P450 2E1 mRNAs in humans
Mario Bauer, 1 Olf Herbarth, 1 Gabi Aust 2 and Carolin Graebsch 1
1UFZ – Centre for Environmental Research Leipzig-Halle, Department of Human Exposure Research and Epidemiology,Permoser street 15, 04318 Leipzig, Germany; 2Research Laboratories, Department of Surgery, University of Leipzig
Received 9 March 2005; accepted 23 June 2005
Abstract
Human cytochrome P450 2E1 (CYP2E1) is a phase I metabolizing enzyme. It is involved in the
biotransformation of xenobioticsand endogenous substrates. Inter-individual genetic polymorphisms of the CYP2E1 gene are associated with different cancerdiseases as well as alcohol and nicotine dependence. We report here for the first time three novel alternative spliced mRNAtranscripts which are more frequently present in lung carcinoma cell lines as in hepatocyte cell lines. They are unexpecteddetectable in blood leukocytes from healthy volunteers but not in normal and cancerous lung tissue. The full-length wildtypetranscript of CYP2E1 is described to be concomitant to an alternatively spliced mRNA transcript. Stimulation with CYP2E1-inducing agents did not change the splicing transcript pattern. The three splicing variants should lead to truncated non- functionalproteins. Thus the genetic diversity of CYP2E1 is additionally extended at the transcriptional level of gene expression. Thephysiological role of the splicing variants is not known, yet, but they seem to be related to the carcinogenic property of the celllines. (Mol Cell Biochem 280: 201–207, 2005)
