期刊
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
卷 17, 期 16, 页码 -出版社
MDPI
DOI: 10.3390/ijerph17165865
关键词
1; 4-BQ; oxidative stress; genotoxicity; hematopoietic stem; progenitor cells; lineage-directed strategy
资金
- FRGS (UKM) [FRGS/1/2016/SKK13/UKM/03/1]
Hematopoietic stem/progenitor cells (HSPCs) are susceptible to benzene-induced genotoxicity. However, little is known about the mechanism of DNA damage response affecting lineage-committed progenitors for myeloid, erythroid, and lymphoid. Here, we investigated the genotoxicity of a benzene metabolite, 1,4-benzoquinone (1,4-BQ), in HSPCs using oxidative stress and lineage-directed approaches. Mouse bone marrow cells (BMCs) were exposed to 1,4-BQ (1.25-12 mu M) for 24 h, followed by oxidative stress and genotoxicity assessments. Then, the genotoxicity of 1,4-BQ in lineage-committed progenitors was evaluated using colony forming cell assay following 7-14 days of culture. 1,4-BQ exposure causes significant decreases (p< 0.05) in glutathione level and superoxide dismutase activity, along with significant increases (p< 0.05) in levels of malondialdehyde and protein carbonyls. 1,4-BQ exposure induces DNA damage in BMCs by significantly (p< 0.05) increased percentages of DNA in tail at 7 and 12 mu M and tail moment at 12 mu M. We found crucial differences in genotoxic susceptibility based on percentages of DNA in tail between lineage-committed progenitors. Myeloid and pre-B lymphoid progenitors appeared to acquire significant DNA damage as compared with the control starting from a low concentration of 1,4-BQ exposure (2.5 mu M). In contrast, the erythroid progenitor showed significant damage as compared with the control starting at 5 mu M 1,4-BQ. Meanwhile, a significant (p< 0.05) increase in tail moment was only notable at 7 mu M and 12 mu M 1,4-BQ exposure for all progenitors. Benzene could mediate hematological disorders by promoting bone marrow oxidative stress and lineage-specific genotoxicity targeting HSPCs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据