DNA Damage Potential of Low Level Toluene Exposure in Mice

碩士 === 國立陽明大學 === 環境與職業衛生研究所 === 99 === Toluene is derived mostly from petroleum and is widely used in the industry as a solvent. In the human body, toluene is absorbed primarily by the lungs. After absorption, it is distributed to all tissues, largely in those with high fat content, such as brain a...

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Bibliographic Details
Main Authors: Ting-Ying Liao, 廖庭瑛
Other Authors: Tsung-Yun Liu
Format: Others
Language:zh-TW
Published: 2011
Online Access:http://ndltd.ncl.edu.tw/handle/57811558456414553267
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Summary:碩士 === 國立陽明大學 === 環境與職業衛生研究所 === 99 === Toluene is derived mostly from petroleum and is widely used in the industry as a solvent. In the human body, toluene is absorbed primarily by the lungs. After absorption, it is distributed to all tissues, largely in those with high fat content, such as brain and bone marrow. Toluene can be metabolized by the cytochrome P450 system in the liver and is excreted through the urine as hippuric acid. Many studies suggest that exposure to toluene may cause malfunctions or structural changes in the central nervous system, such as: headaches, behavior changes, and hearing and visual dysfunction. In the liver, only a small fraction of toluene is metabolized to cresol, which forms an intermediate semiquinone. Semiquinone with an unpaired and extra electron combines with other molecules to generate ROS. However, it is not known whether toluene exposure is associated with DNA damage in the brain. Many studies suggest that allergic individuals exposed to volatile organic compounds (VOC, such as toluene or formaldehyde) will develop multiple chemical sensitivities. Exposure to VOCs are more sensitive for the allergic individuals , in addition, it is not known whether damage occurs more easily with exposure to low level toluene. This study hypothesizes that low level toluene exposure causes brain DNA damage, in addition, allergic individuals are more sensitive than normal people. Eight -week-old Balb/c mice were exposed to 0 (control group) or 25 (exposure group) ppm toluene in an inhalation chamber for six hours a day, five days per week for four weeks. Another group of mice were immunized with ovalbumin and treated similarily. At the end of the study, the brain was removed, and the hippocampus, cerebellum, cerebral cortex, and blood were collected. DNA damage was then evaluated by comet assay. In addition, the content of brain-derived neurotrophic factors in hippocampus was evaluated. The results of this study indicated that low level toluene induced DNA damage in the hippocampus of normal animals. On the other hand, in allergy group, low level toluene exposure lead to DNA damage in leukocytes as well as in the hippocampus. At the same toluene concentration, damage was less in the allergy group than in the normal group. The results are linked to brain BDNF content.