Protective role of metallothionein (I/II) against pathological damage and apoptosis induced by dimethylarsinic acid.
OBJECTIVE
To better clarify the main target organs of dimethylarsinic acid toxicity and the role of metallothionein (MTs) in modifying dimethylarsinic acid (DMAA) toxicity.


METHODS
MT-I/II null (MT(-/-)) mice and the corresponding wild-type mice (MT(+/+)), six in each group, were exposed to DMAA (0-750 mg/kg body weight) by a single oral injection. Twenty four hours later, the lungs, livers and kidneys were collected and undergone pathological analysis, induction of apoptotic cells as determined by TUNEL and MT concentration was detected by radio-immunoassay.


RESULTS
Remarkable pathological lesions were observed at the doses ranging from 350 to 750 mg/kg body weight in the lungs, livers and kidneys and MT(+/+) mice exhibited a relatively slight destruction when compared with that in dose matched MT(-/-) mice. The number of apoptotic cells was increased in a dose dependent manner in the lungs and livers in both types of mice. DMAA produced more necrotic cells rather than apoptotic cells at the highest dose of 750 mg/kg, however, no significant increase was observed in the kidney. Hepatic MT level in MT(+/+) mice was significantly increased by DMAA in a dose-dependent manner and there was no detectable amount of hepatic MT in untreated MT(-/-) mice.


CONCLUSIONS
DMAA treatment can lead to the induction of apoptosis and pathological damage in both types of mice. MT exhibits a protective effect against DMAA toxicity.
Jia
Guang
G
Department of Occupational and Environmental Health Sciences, Health Sciences, School of Public Health, Peking University, Beijing 100083, China. jiaguangjia@yahoo.com.cn
Gu
Yi-Qun
YQ
Chen
Kung-Tung
KT
Lu
You-Yong
YY
Yan
Lei
L
Wang
Jian-Ling
JL
Su
Ya-Ping
YP
Wu
J C Gaston
JC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002101:Cacodylic Acid / Q000633:toxicity*; D006540:Herbicides / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000473:pathology; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D006540:Herbicides; D008668:Metallothionein; D002101:Cacodylic Acid