Sodium selenite enhances glutathione peroxidase activity and DNA strand breaks in hepatoma induced by N-nitrosodiethylamine and promoted by phenobarbital |
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Authors: | C Thirunavukkarasu K Premkumar A K Sheriff D Sakthisekaran |
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Institution: | (1) Department of Medical Biochemistry, Dr. ALM Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India;(2) Present address: Department of Biochemistry, Periyar University, Salem, 636011, Tamil Nadu, India;(3) Department of Genetics, Dr. ALM Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India;(4) Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India |
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Abstract: | An element/compound that acts as an antioxidant as well as, can increase the oxidative stress offers a new approach in differentiation
therapy. Experiments were carried out to determine the effect of selenite on DNA damage and glutathione peroxidase (GPx) activity
in N-nitrosodiethylamine (DEN) induced, phenobarbital promoted rat hepatoma. Supra-nutritional level of selenite (4 ppm) was
supplemented at either, before-initiation/after-initiation and/or during entire period of the study. At the end of experiment
period (20 weeks), extent of DNA damage (alkaline comet assay), selenium concentration, and GPx activity were assessed on
nodular tissue (NL) cells, surrounding liver (SL) cells, and whole liver tissue (control) cells. Hepatic selenium level and
GPx activity were decreased in DEN and PB-administered animals, whereas the DNA damage was found to be increased in both NL
and SL cells compared with control group. However, the DNA damage is more in SL cells than in NL cells. Pre-supplementation
of selenite did not show any difference in DNA (strand breaks) damage, selenium, and GPx activity. Increased hepatic selenium
concentration and GPx activity were observed in both NL and SL cells in post-supplementation and entire period of selenite
supplemented animals compared to DEN + PB treated animals. However, DNA damage was increased in NL but decreased in SL cells.
Supplementation of selenite alone for 16 or 20 weeks had shown increased DNA damage, selenium concentration, and GPx activity
compared to normal control animals. In summary, cancer bearing animals increased DNA damage and decreased Se level and GPx
activity in NL and SL cells and other organs in cancer bearing animals, supplementation of Se further provoked DNA damage
(no change in pretreatment) in NL cells, however it decreased DNA damage SL cells and other organs (kidney, lungs, and spleen).
On the other hand Se levels and GPx activity were increased in NL and SL cells and other organs of Se-supplemented rats (no
difference in group 3 animals). These results demonstrate that, in addition to chemopreventive and chemotherapeutic role of
selenite, it also prevents cellular DNA damage induced in cancerous condition. |
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Keywords: | Selenite Hepatoma DNA damage Comet assay |
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