Acquired tolerance of hepatocellular carcinoma cells to selenium-deficiency : a selective survival mechanism
Author
Irmak, Meliha Burcu
Advisor
Çetin-Atalay, Rengül
Date
2003Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
Selenium-deficiency causes liver necrosis. Selenium is protective against viral
hepatitis and hepatocellular carcinoma (HCC). The underlying molecular
mechanisms of selenium effects are ill-known. In this study in vitro response of
hepatocellular carcinoma-derived cell lines to selenium-deficiency is examined
alone or in conjunction with Vitamin E and Copper/Zinc. Here we show that in
vitro selenium-deficiency in a subset HCC-derived ‘hepatocyte-like’ cell lines
causes oxidative stress and apoptosis. The oxidative stress and consequent cell
death induced by selenium-deficiency on these cells are reverted by the
antioxidant effect of Vitamin E. However, ten among thirteen HCC cell lines are
tolerant to selenium-deficiency and escape its deadly consequences. Nine of ten
tolerant cell lines have integrated hepatitis B Virus (HBV) DNA in their genomes,
and some display p53-249 mutation, indicating past exposure to HBV or
aflatoxins, established factors for oxidative stress and cancer risk. Thus, as
demonstrated by the gain of survival capacity of apoptosis sensitive cell lines with
Vitamin E, such malignant cells have acquired a selective survival advantage that
is prominent under selenium-deficient and oxidative stress conditions.