Basic Research
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 1, 2004; 10(1): 91-95
Published online Jan 1, 2004. doi: 10.3748/wjg.v10.i1.91
Protective role of metallothionein (I/II) against pathological damage and apoptosis induced by dimethylarsinic acid
Guang Jia, Yi-Qun Gu, Kung-Tung Chen, You-Yong Lu, Lei Yan, Jian-Ling Wang, Ya-Ping Su, J. C. Gaston Wu
Guang Jia, Lei Yan, Jian-Ling Wang, Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100083, China
Yi-Qun Gu, Department of Pathology, Hepingli Hospital, Beijing 100013, China
Kung-Tung Chen, Department of General Education, Ming-hsin University of Science and Technology, Taiwan, China
You-Yong Lu, School of Oncology, Peking University, Beijing 100034, China
Ya-Ping Su, J. C. Gaston Wu, Department of Chemistry, National Taiwan Normal University, Taiwan, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Guang Jia, Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, 38 Xue Yuan Road, Beijing 100083, China.
Telephone: +86-10-82801523 Fax: +86-10-62015583
Received: July 4, 2003
Revised: July 20, 2003
Accepted: July 24, 2003
Published online: January 1, 2004

AIM: 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.

CONCLUSION: 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.

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