Hepatocellular carcinoma / low iron diet

[Ironjustic]

<<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=2E, 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 =B1 4.6/105 dG) significantly decreased to
almost normal levels (2.2 =B1 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

[outsor]

It is important to note that the disorder required to allow
elevated iron levels and higher risk of cancer is not itself
caused by iron, another dog and tail story.

[Ironjustic]

<<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]

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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

[outsor]

"Excess hepatic iron may be both directly and indirectly
carcinogenic. "

There is that old "min, opt, and max" thing again; "excess" is
the operative word. In this rat study excess at a very high
level was induced by giving them very high levels of an iron
compound. Moderation in all things, including iron is always
wise, including that found in animal sources.