期刊
TOXICOLOGY LETTERS
卷 225, 期 3, 页码 413-421出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2014.01.010
关键词
Tributyltin; Germline; DNA damage; Checkpoint pathway; Apoptosis; Cell cycle arrest
类别
资金
- Fundamental Research Funds for the Central Universities of People's Republic of China [2010121091]
- Programme of Introducing Talents of Discipline to Universities [B06016]
- National Natural Science Foundation of China [81000740, 81071384, 81171596]
- NIH National Center for Research Resource, USA
Tributyltin (TBT), one of the environmental pollutants, has been shown to impact the reproduction of animals. However, due to the lack of appropriate animal model, analysis of the affected molecular pathways in germ cells is lagging and has been particularly challenging. In the present study, we investigated the effects of tributyltin chloride (TBTCL) on the nematode Caenorhabditis elegans germline. We show that exposure of C. elegans to TBTCL causes significantly elevated level of sterility and embryonic lethality. TBTCL exposure results in an increased number of meiotic DNA double-strand breaks in germ cells, subsequently leading to activated DNA damage checkpoint. Exposing C. elegans to TBTCL causes dose-and time-dependent germline apoptosis. This apoptotic response was blocked in loss-of-function mutants of hus-1 (op241), mrt-2 (e2663) and p53/cep-1 (gk138), indicating that checkpoints and p53 are essential for mediating TBTCL-induced germ cell apoptosis. Moreover, TBTCL exposure can inhibit germ cell proliferation, which is also mediated by the conserved checkpoint pathway. We thereby propose that TBT exhibits its effects on the germline by inducing DNA damage and impaired maintenance of genomic integrity. Index Descriptors and Abbreviations: TBTCL, tributyltin chloride; C. elegans, Caenorhabditis elegans; NGM, nematode growth medium; DMSO, dimethyl sulfoxide; DAPI, 4', 6-diamidino-2-phenylindole; DSBs, DNA double-strand breaks. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.
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