DNA damage and cytotoxicity in pancreatic beta-cells expressing human CYP2E1

Biochemical Pharmacology
Diane J Lees MurdockChristopher R Barnett

Abstract

Epidemiological studies have identified nitrosamines as a risk factor for Type I (insulin dependent) diabetes mellitus. These compounds require bioactivation by cytochrome P450 2E1 (CYP2E1) for exertion of their toxic effects. Two mammalian insulin secreting pancreatic beta-cell lines BRIN BD11h2E1 and INS-1h2E1, which express human full length CYP2E1 cDNA, were used to elucidate the role of CYP2E1-mediated nitrosamine bioactivation in pancreatic beta-cell dysfunction and destruction. These cell lines were shown to metabolise dimethylnitrosamine to produce formaldehyde at rates of 3.41 +/- 0.24 and 3.65 +/- 0.26 nmol/minmg microsomal protein, respectively. Following incubation with various concentrations of the nitrosamines dimethylnitrosamine, N-nitrosopyrrolidine and 1-nitrospiperidine, all of which are bioactivated by CYP2E1, cytotoxicity and DNA damage were assessed using either the neutral red assay or comet assay respectively. Exposure of CYP2E1 expressing cells to nitrosamines resulted in significant dose-dependent decreases in cell viability, which were not seen in cells which did not express CYP2E1. Following culture with nitrosamine concentrations as low as 2.5mM 1-nitrosopiperidine, cell viability was significantly l...Continue Reading

References

Oct 1, 1975·The Journal of Pharmacy and Pharmacology·C Ioannides, D V Parke
Jan 1, 1990·Chemico-biological Interactions·C R BarnettC Ioannides
Oct 1, 1990·The Journal of Clinical Endocrinology and Metabolism·B J SongP Saenger
Mar 1, 1988·Experimental Cell Research·N P SinghE L Schneider
Nov 1, 1982·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M Ingelman-Sundberg, A L Hagbjörk
Nov 15, 1982·Biochemical Pharmacology·W J Malaisse
Dec 8, 1980·Life Sciences·D Y Lai, J C Arcos
Feb 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·W J MalaisseD G Pipeleers
Jan 1, 1994·Drug Metabolism Reviews·F J Gonzalez, H V Gelboin
Apr 1, 1993·The Journal of Pathology·J R FosterJ M Braganza
Sep 1, 1995·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·A Irizar, C Ioannides
Feb 17, 1996·Lancet·P DandonaT Nicotera
Feb 23, 1996·Journal of Chromatography. B, Biomedical Applications·A ZerilliJ F Ménez
May 15, 1998·Alcoholism, Clinical and Experimental Research·I G KessovaC S Lieber
Jul 29, 1998·Free Radical Biology & Medicine·A R CollinsM Dusinská
Aug 11, 1998·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·S S Hecht, D Hoffman
Sep 15, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y TanakaR P Robertson
Nov 19, 2002·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Alexis B UlrichParviz M Pour
Jan 22, 2003·British Journal of Clinical Pharmacology·Zaiqi WangJ C Gorski
May 14, 2003·European Journal of Clinical Pharmacology·Vincent HaufroidDominique Lison
May 27, 2003·Diabetes Care·Karin B MichelsUNKNOWN Nurses' Health Study
Dec 5, 2003·Journal of the National Cancer Institute·Kazem ZendehdelWeimin Ye
Apr 24, 2004·Biochemical Pharmacology·Diane J Lees MurdockChristopher R Barnett
Jul 7, 2007·Critical Reviews in Toxicology·T WangH M Mehendale

❮ Previous
Next ❯

Citations

Dec 6, 2006·Molecular and Cellular Biochemistry·De-Fu HouZhu-Chu Chen
Nov 3, 2005·Environmental Health Perspectives·Mary H WardUNKNOWN International Society for Environmental Epidemiology
Oct 4, 2011·European Journal of Endocrinology·Tao LiuWen-Hua Ling
Apr 14, 2010·Reviews on Environmental Health·Mary H Ward
May 22, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Nuria ArranzPaloma Morales
Nov 8, 2006·Diabetes/metabolism Research and Reviews·Steven PattersonNeville H McClenaghan
Sep 6, 2013·Biochimica Et Biophysica Acta·Srividya VasuPeter R Flatt
Dec 21, 2014·Journal of Molecular Endocrinology·Srividya VasuPeter R Flatt
Apr 17, 2007·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·N ArranzP Morales
Dec 7, 2017·Chinese Journal of Integrative Medicine·Li-Rui TangHai-Nan Wang
Mar 16, 2013·Biological Chemistry·Srividya VasuPeter R Flatt
Feb 21, 2013·Human & Experimental Toxicology·R K SharmaB Sharma
Feb 26, 2010·Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes·Avinash M Topè, Phyllis F Rogers

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.