| Summary: | 碩士 === 國立陽明大學 === 環境與職業衛生研究所 === 98 === Toluene is mostly derived from petroleum and being widely used in the industry as a solvent. Toluene is mainly absorbed by the human body via the lungs and the gastrointestinal tract but rarely through the skin. After Toluene is absorbed, it is spread to all tissues inside the human body, largely in those with high fat content, such as brain and bone marrow. Toluene can be metabolize by the cytochrome P450 system in the liver; about 60-70% is excreted through the urine as hippuric acid and the rest is carried out by the respiratory tract in its original form.
Many studies suggest that exposure to toluene may cause malfunction or structural changes of the central nervous system, such as: headaches, nervous behavior, hearing and visual dysfunction. Long term exposure to toluene can even lead to permanent nerve damages, but the toluene-induced genetic toxicity, whether in animal or human studies, are unclear. In the liver, only a few (less than 5%) of toluene is metabolized to para-cresol or ortho-cresol, both of which would form an intermediate semiquinone; semiquinone with an unpaired electron, easily to generate ROS (O2-‧, H2O2). Whether the formation of these ROS is related to toluene genetic toxicity is not clear.
This study assumes that acute high dose toluene exposure can lead to genotoxic and oxidative DNA damage in the brain of experimental animals. Seven-week-old SD rats were intraperitoneally injected with toluene dissolved in corn oil (0.5 g/kg and 1.5 g/kg), the control group were injected with 0.9% saline dissolved in corn oil. Two hours later, the animals were sacrificed and the hippocampus, cerebellum, cortex, liver and blood were removed, then DNA damages were evaluated using comet assay. In addition, the oxidation of DNA damage were examined utilizing comet assay incorporated with Fpg enzyme. The results demonstrated that acute administration of high-dose toluene to experimental animals lead to direct DNA damage in hippocampus, cerebellum and cortex, and the oxidative DNA damage in hippocampus, cerebellum, liver and white blood cell. The toluene-induced oxidative DNA damage was also observed in cortex, but not statistically significant. On the other hand, acute exposure to low dose of toluene can also cause direct DNA damage in the hippocampus and cerebellum and oxidative DNA damage in the cerebellum and cortex.
This study suggests that acute toluene exposure to rats causes brain genotoxicity and oxidative DNA damage.
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