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(41-29) Human and Ecological Risk Assessment: Animal Strain as a Source of Confounding. Stedeford, Todd*,1,2, Banasik, Marek1,2, Suchecki, Tomasz1, 1 Institute of Environmental Engineering, Zabrze, Poland2 Laboratory of Molecular Clinical Chemistry, Uji, Japan ABSTRACT- The safe-levels of allowable chemical emissions in the environment are generally determined using animals. However, toxicological data derived from animal models, particularly rodents, have limitations in their ability to predict the risk of exposure not only to humans, but also the multitude of organisms in the ecosystem, due to differences in exposure, physiology, metabolism, and repair enzyme systems. The purpose of this study was to characterize the differences that exist in the enzymatic capacity of key enzymes responsible for the clearance of superoxide anion and the oxidized DNA base 8-hydroxy-2'-deoxyguanosine (oxo8dG), superoxide dismutase (SOD) and 8-oxoguanosine DNA-glycosylase (Ogg1), respectively. Cerebellum (CB) and caudate putamen (CP), from male C57BL/J, Balb/c, and ICR mice were analyzed. There was no significant difference in the activity or protein level of Ogg1 in the CB; however, the activity of Ogg1 in the CP of ICR mice was 34 and 31% lower than C57BL/J and Balb/c, respectively. SOD activity in the CB was twice as high in C57BL/J mice versus Balb/c or ICR. SOD activity in the CP of C57BL/J mice was four fold higher than in Balb/c and ICR. The relevance of these differences was determined by measuring levels of oxo8dG, an oxidized 2-deoxyguanosine formed by reactive oxygen species, such as superoxide anion. The levels of oxo8dG in the CB and CP of C57BL/J mice were nearly two times the values in both regions of Balb/c and ICR mice. Based on these results, it is argued that risk estimations based strictly on rodent bioassay data could be unnecessarily high in some cases and, in others, deceptively low and not protective of the genera in the ecosystem. Key words: Animal Models, Mechanisms, DNA Damage, DNA Repair |
