کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5558308 | 1561138 | 2017 | 9 صفحه PDF | دانلود رایگان |
- Nucleated bone marrow cell count recovered after 7Â days post-FA and/or BZ exposure.
- CFU-GM showed an increase in colonies and 8-OHdG after 7Â days post-FAÂ +Â BZ exposure.
- Levels of ROS in CFU-GM and BFU-E were increased by FA or FAÂ +Â BZ during recovery.
- Levels of GM-CSF and EPOR were suppressed after 7Â days post-FA or FAÂ +Â BZ exposure.
- Co-exposure was more potent for some endpoints and may pose a greater leukemia risk.
Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3Â mg/m3 FA for 2Â weeks, mimicking occupational exposure, and were monitored for another 7Â days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently. After 7-day recovery, colonies of progenitors for CFU-GM and BFU-E, and nucleated bone marrow cells in FA-exposed mice were comparable to controls, although they were significantly reduced during exposure. Levels of reactive oxygen species (ROS) and 8-hydroxy-2â²-deoxyguanosine (8-OHdG) in CFU-GM and BFU-E from FA-exposed mice were higher than controls, although the increase in 8-OHdG was not significant. Granulocyte-macrophage colony stimulating factor (GM-CSF) level in the FA group was lower than controls, but the expression level for the receptor was not upregulated. It suggests that HSCs/HPCs in FA-exposed mice respond to a small amount of GM-CSF and proliferate rapidly, which may cause a possible risk of expansion of abnormal stem/progenitor cell clones. FA co-exposure with BZ was more potent for promoting CFU-GM formation and inducing ROS in BFU-E and 8-OHdG in CFU-GM during the post-exposure period. The compensation of myeloid progenitors with elevated ROS and 8-OHdG may lead to a risk of transforming normal HSCs/HPCs to leukemic stem/progenitor cells. Thus, co-exposure may pose a greater leukemia risk.
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Journal: Toxicology and Applied Pharmacology - Volume 324, 1 June 2017, Pages 36-44