期刊
TOXICOLOGICAL SCIENCES
卷 126, 期 2, 页码 569-577出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfs001
关键词
benzene; benzoquinone; fetal; blood cells; reactive oxygen species; DNA damage
类别
资金
- Canadian Institutes for Health Research [MOP 394-896]
In utero exposure to environmental carcinogens, including the ubiquitous pollutant benzene, may cause DNA damage in the fetus, leading to an increased risk for the development of childhood cancer. Benzene metabolite-induced DNA double-strand breaks (DSBs) may undergo erroneous repair, leading to chromosomal aberrations including chromosomal inversions and translocations. In this study, fetal murine hematopoietic cells from pZK1 transgenic mice were exposed to p-benzoquinone (BQ), a toxic metabolite of benzene, and assessed for DNA recombination, DNA damage including DNA DSBs as measured by gamma-H2A.X foci and oxidative DNA damage, and reactive oxygen species (ROS) production. The pZK1 transgenic mouse model contains a DNA construct allowing for the detection of intrachromosomal recombination events. Using this model, a significant increase in recombination was observed following exposure to BQ (25 and 50 mu M) at various time points. Additionally, increased gamma-H2A.X foci were observed following exposure to 25 mu M BQ for 30 min, 45 min, and 1 h, whereas this exposure did not significantly increase oxidative DNA damage. Pretreatment with 400 U/ml polyethylene glycol-conjugated-catalase attenuated increases in DNA recombination as compared with treatment with BQ alone. An increase in ROS production (30 min and 1 h), as measured by dichlorodihydrofluorescein diacetate fluorescence, was also observed following exposure to 25 mu M BQ. These studies indicate that BQ is able to induce DNA damage and recombination in fetal liver cells and that ROS may be important in the mechanism of toxicity.
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