Induction of germline cell cycle arrest and apoptosis by sodium arsenite in Caenorhabditis elegans.
The nematode Caenorhabditis elegans has been shown to be a model organism in studying aquatic toxicity. Although epidemiological studies have shown that arsenic is teratogenic and carcinogenic to humans, the lethality assay indicated that C. elegans is less sensitive to inorganic arsenic than any other organisms that have been tested thus far. In the present study, we used the more malleable germline of C. elegans as an in vivo system to investigate the genotoxic effects of arsenite. After animals were exposed to sodium arsenite at concentrations ranging from 1 microM to 0.5 mM, mitotic germ cells and germline apoptosis were scored after DAPI staining and acridine orange vital staining, respectively. DMSO rescue experiments were performed by exposing C. elegans to 0.01 mM arsenite in the presence of DMSO (0.1%) for 24 h, and reactive oxygen species (ROS) were semiquantified by CM-H(2)DCFDA vital staining. The results indicated that arsenic exposure reduced the brood size of C. elegans and caused mitotic cell cycle arrest and germline apoptosis, which, to some extent, exhibited a concentration- and time-dependent manner. The addition of 0.1% DMSO completely rescued arsenic-induced cell cycle arrest and partially suppressed germline apoptosis. Furthermore, treatment of animals with arsenite at a dose of 0.01 mM significantly increased ROS production in the intestine, which could be reduced by DMSO treatment. The present study also indicated that C. elegans might be used as an in vivo model system to study the mechanisms of arsenic-induced genotoxic effects.
Wang
Shunchang
S
Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, Anhui 230031, People's Republic of China.
Zhao
Ye
Y
Wu
Lijun
L
Tang
Mingli
M
Su
Caixing
C
Hei
Tom K
TK
Yu
Zengliang
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D002453:Cell Cycle / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005854:Germ Cells / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017670:Sodium Compounds / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
D018053:Arsenites; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; C017947:sodium arsenite; D004121:Dimethyl Sulfoxide