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Medical Forum / General / General / December 2005Hepatocellular carcinoma / low iron diet
<<snip>> None of these patients developed hepatocellular carcinoma (HCC). <<snip>> http://cancerres.aacrjournals.org/cgi/content/abstract/61/24/8697 Clinical Investigations Normalization of Elevated Hepatic 8-Hydroxy-2'-Deoxyguanosine Levels in Chronic Hepatitis C Patients by Phlebotomy and Low Iron Diet1 Junji Kato, Masayoshi Kobune, Tokiko Nakamura, Ganji Kuroiwa, Kohichi Takada, Rishu Takimoto, Yasuhiro Sato, Koshi Fujikawa, Minoru Takahashi, Tetsuji Takayama, Tatsuru Ikeda and Yoshiro Niitsu2 Fourth Department of Internal Medicine [J. K., T. N., G. K., K. T., R. T., Y. S., K. F., M. T., T. T., Y. N.] and Department of Molecular Medicine [M. K.], Sapporo Medical University School of Medicine, and Department of Clinical Pathology, Sapporo Medical University Hospital [T. I.], Sapporo 060-8543, Japan Accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA, which may result from the continuous reactive oxygen species (ROS) generation associated with chronic inflammation, has been reported in various human preneoplastic lesions and in cancerous tissues. However, no direct causative relationship between the 8-OHdG formation and carcinogenesis has been thus far demonstrated in humans. Directly proving the causality requires showing that depletion of 8-OHdG levels in tissue by interfering with ROS generation results in a reduction in cancer. Chronic hepatitis C virus (HCV) infection is associated with a high risk of hepatocellular carcinoma (HCC). Several studies on patients with chronic HCV have shown that hepatic iron overload is attributable to liver injury and that iron depletion improved serum aminotransferase levels. Excess iron is known to generate ROS within cells, which causes mutagenic lesions, such as 8-OHdG. In this study, therefore, we have evaluated whether therapeutic iron reduction (phlebotomy and low iron diet) with a long-term follow-up (6 years) would decrease the hepatic 8-OHdG levels and the risk of HCC development in patients with chronic HCV. Patients (34) enrolled were those who had undergone standard IFN therapy but had no sustained response. Quantitative immunohistochemistry using the KS-400 image analyzing system and electrochemical detection was used for 8-OHdG detection. With this treatment, elevated hepatic 8-OHdG levels in patients with chronic hepatitis C (8.3 ± 4.6/105 dG) significantly decreased to almost normal levels (2.2 ± 0.9/105 dG; P < 0.001) with concomitant improvement of hepatitis severity, including fibrosis, whereas HCV titers were unaffected. None of these patients developed HCC. Thus, long-term iron reduction therapy in patients with chronic hepatitis C may potentially lower the risk of progression to HCC. Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking <<snip>> direct hepatocarcinogenic effect of free iron is mediated by the generation of oxygen reactive species and oxidative damage that are mutagenic and carcinogenic <<snip>> 1: Toxicology. 2005 Dec 5; [Epub ahead of print] Links Hepatocellular carcinoma caused by iron overload: A possible mechanism of direct hepatocarcinogenicity. Asare GA, Mossanda KS, Kew MC, Paterson AC, Kahler-Venter CP, Siziba K. MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa. BACKGROUND/AIMS: Excess hepatic iron may be both directly and indirectly carcinogenic. The aim of this study was to determine if generation of reactive oxygen species and the resulting oxidative damage induced by free hepatic iron is directly hepatocarcinogenic. METHODS: Sixty male Wistar albino rats were iron-loaded by ferrocene supplementation of their diet. Biochemical parameters of oxidative damage and lipid peroxidation, DNA unwinding and strand breaks, and the Ames Mutagenesis Test were measured at 4 monthly intervals and correlated with the degree of hepatic iron overload, the presence of iron-free preneoplastic foci in the liver, and the development of hepatocellular carcinoma in comparison with 60 control rats. RESULTS: Levels of lipid hydroperoxides, malonaldehyde, 8-isoprostane and 8-hydroxy-2'-deoxyguanosine increased, reaching peak concentrations at 20-24 months, and correlating with an increase in the rate of DNA unwinding, strand breaks, and positive Ames Tests. Iron-free neoplastic foci became evident at 16 months and thereafter increased in number. Preneoplastic foci were present in five of eight rats remaining at 32 months and HCC had developed in one of the five. CONCLUSIONS: Our findings are compatible with the hypothesis that the direct hepatocarcinogenic effect of free iron is mediated by the generation of oxygen reactive species and oxidative damage that are mutagenic and carcinogenic. PMID: 16337327 [PubMed - as supplied by publisher] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking |
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