Role of cytokines in non-genotoxic hepatocarcinogenesis: cause or effect?

Toxicology Letters
R A RobertsG Orphanides

Abstract

Chemicals with the potential to cause cancer through damaging DNA can be readily identified in a range of in vitro screens that detect genotoxicity. However, many carcinogens are non-genotoxic yet cause rodent tumours, particularly in the liver. Some non-genotoxic carcinogens such as the peroxisome proliferators (PPs) act directly to cause liver growth and proliferation, whereas others such as carbon tetrachloride cause liver damage, followed by regenerative hyperplasia. Current data support a role for cytokines such as tumour necrosis factor alpha (TNFalpha) and interleukin 1 (IL1) in hepatocarcinogenesis. However, these data give rise to conflicting hypotheses; in some experimental models, TNFalpha appears to mediate damage, whereas in others it is postulated to play a role in tissue repair. Recently, we have shown that TNFalpha acting via TNFalpha receptor 1 and p38 MAP kinase suppresses hepatocyte apoptosis. However, when new protein synthesis is disabled, TNFalpha becomes a death signal. An understanding of the role of cytokines in rodent hepatocarcinogenesis will allow the development of markers that can be used to identify, at an early stage, those chemicals with the potential to induce rodent tumours.

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·F A OberhammerR Schulte-Hermann
Sep 11, 1990·European Journal of Biochemistry·K Decker
Jun 1, 1996·Critical Reviews in Toxicology·W W HuberR Schulte-Hermann
Apr 1, 1996·Human & Experimental Toxicology·C C Boyle
Nov 1, 1996·International Archives of Allergy and Immunology·L Rink, H Kirchner
Aug 1, 1997·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·R A RobertsT L Goldsworthy
Jul 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H C Pitot
Jul 30, 1999·Carcinogenesis·R A Roberts, I Kimber
Nov 26, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D A WestR A Roberts
Feb 3, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R A RobertsS C Cosulich
Feb 26, 2000·Carcinogenesis·S W Lowe, A W Lin

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Citations

Sep 18, 2007·Archives of Toxicology·Hee-Young SonJae-Ho Yang
Aug 24, 2002·Pharmacology & Toxicology·Jason D Oliver, Ruth A Roberts
Aug 15, 2013·Marine Environmental Research·Francesco Regoli, Maria Elisa Giuliani
Sep 7, 2006·Critical Reviews in Toxicology·Ivan RusynMichael L Cunningham
Apr 24, 2003·Critical Reviews in Toxicology·Lutz W D WeberAndreas Stampfl
Aug 6, 2002·Molecular and Cellular Endocrinology·Frank J Gonzalez
Jun 10, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ivan RusynMartyn T Smith

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