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The effect of ethanol and nitric oxide on the N-nitrosodimethylamine formation in HepG2 cells overexpressing CYP2E1

Jakub Jabloski

Department of Toxicology, Medical University of Bialystok, Bialystok, Poland; Department of Toxicology, Medical Academy of Bialystok, Mickiewicza 2c str., 15-222 Bialystok, Polandtoksykologia{at}wp.pl

Adam Holownia

Department of Clinical Pharmacology, Medical University of Bialystok, Bialystok, Poland

Ewa Jabloska

Department of Immunology, Medical University of Bialystok, Bialystok, Poland

Janina Moniuszko-Jakoniuk

Department of Toxicology, Medical University of Bialystok, Bialystok, Poland

Jan Braszko

Department of Clinical Pharmacology, Medical University of Bialystok, Bialystok, Poland

Jolanta Iwanowska

Center of Oncology, Radiotherapy Division, Medical University of Bialystok, Bialystok, Poland

Magda Marciczyk

Department of Immunology, Medical University of Bialystok, Bialystok, Poland

The influence of lipopolysaccharide (LPS) and the nitric oxide synthase (iNOS) inhibitor-N-nitro-L-arginine on the formation of N-nitrosodimethylamine (NDMA) by HepG2 cells, engineered to overexpress CYP2E1, was assessed and compared with data from empty vector-transfected cells. HepG2 cells produced significant amounts of NDMA but its levels in the culture media of cells overexpressing CYP2E1 was significantly lower than in empty-vector transfected cells. LPS increased the formation of NDMA, the expression of the iNOS and the production of the nitric oxide (NO). On the other hand, L-NAME significantly decreased NDMA levels. The results above indicate that the synthesis of NDMA by HepG2 cells depends on NO production. Furthermore, ethanol did not affect iNOS expression but decreased NDMA levels in CYP2E1-transfected cells below the detection limit. It is probably caused by the increased N-nitrosodimethylamine metabolism. In conclusion, HepG2 cells' ability to synthesize NO with simultaneous CYP2E1 activation may lead to an increase of carcinogenic products of the NDMA metabolism.

Key Words: CYP2E1 • ethanol • HepG2 cells • N-nitrosodimethylamine • nitric oxide

Human & Experimental Toxicology, Vol. 24, No. 9, 447-452 (2005)
DOI: 10.1191/0960327105ht557oa


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