1 AIT Asian Institute of Technology

Effects of cadmium on DNA damage and expression of repair gene

AuthorGotovdorj, Tuvshinjargal
Call NumberAIT Thesis no.EV-05-31
NoteA thesis submitted in partial fulfillment of the requirements for the degree of Master of Science AIT THESIS No. AIT Library 2 6 SEP 2005 ~©~~w~~ Inter-University Program on Environmental Toxicology, Technology and Management
PublisherAsian Institute of Technology
AbstractCadmium is a highly toxic heavy metal; however it has been used worldwide. It has been classified a human carcinogen by IARC. Cadmium is genotoxic substance due to it can cause damage to DNA and chromosome. In this study, the effects of cadmium treatment on DNA damage and repair were studied in the human lymphocytes. The dose-response relationship between cadmium treatment and DNA strand breaks was studied in the human lymphocytes treated with 5, 10, 25, 50 and 100M cadmium. Using comet assay, the effects of cadmium treatment at various concentrations caused a significant induction of DNA strand breaks in a dose-dependent manner up to 50M and slightly increased further at 100M in the human lymphocytes. A The time-course of cadmium treatment on an induction of DNA strand breaks was carried out in lymphocytes treated with cadmium for 2, 4 and 24 hours. The effects of cadmium on the DNA strand breaks were also observed in the timedependent manner in the human lymphocytes. The induction of DNA strand breaks indicated a percentage of increase from control was highest at 4 hours following cadmium treatment at all test concentrations, and then dramatically decreased towards 24 hours of treatment. Cadmium treatment at 50M for 4 hours was then selected as the optimum dose and time of cadmium on the DNA damage. The effect of cadmium treatment on the oxidized base DNA damage was studied in human lymphocytes treated at 50M cadmium for 4 hours by comet assay with formamidopyrimidine-DNA-glycosylase (Fpg). The results showed that cadmium significant increased the Fpg-sensitive sites in the human lymphocytes by 1.4-fold (P<0.05), compared to control. Cadmium can cause oxidized base DNA damage. The alterations of repair gene (hOGG1) and metallothionein (MT) gene expression were studied in human lymphocytes treated with 50M cadmium for 4 hours by Reverse-Transcriptase and Polymerase Chain Reaction (RT-PCR). Cadmium induced MT mRNA expression by 1.62-fold (P<0.01) from control. In contrast, cadmium treatment resulted in decrease in the levels of hOGG1 by 1.67-fold (P<0.01), compared to control. In conclusion, the present study demonstrated that cadmium significantly increased DNA strand breaks in human lymphocytes in a dose and time-dependent. In addition, a significant increase in oxidized base damage indicated as Fpg-sensitive base was in accordance with the reduction of repair gene (hOGG1) in human lymphocytes treated with cadmium. Therefore, cadmium can cause genotoxic to human lymphocytes possibly by induction of oxidative DNA damage and of DNA repair inhibition.
Year2005
TypeThesis
SchoolSchool of Environment, Resources, and Development (SERD)
DepartmentDepartment of Energy and Climate Change (Former title: Department of Energy, Environment, and Climate Change (DEECC))
Academic Program/FoSEnvironmental Engineering and Management (EV)
Chairperson(s)Panida Navasumrit;Preeda Parkpian;
Examination Committee(s) Piyajit Watcharasit;
Scholarship Donor(s)Her Majesty The Queen of Thailand ;
DegreeThesis (M. Eng.) -- Asian Institute of Technology, 2005


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