Metallothionein (I/II) suppresses genotoxicity caused by dimethylarsinic acid

  • Authors:
    • Guang Jia
    • Hideko Sone
    • Noriko Nishimura
    • Masahiko Satoh
    • Chiharu Tohyama
  • View Affiliations

  • Published online on: August 1, 2004     https://doi.org/10.3892/ijo.25.2.325
  • Pages: 325-333
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Arsenic is an environmental chemical of considerable concern due to its association with an increased risk of human cancer. Dimethylarsinic acid (DMAA) is one of the major methylated metabolites of ingested arsenicals in most mammals. To better clarify the role of metallothionein (MT) in modifying DMAA genotoxicity, MT-I/II null mice, and the corresponding wild-type mice, were exposed to DMAA (0, 188, 375 or 750 mg/kg body weight) via a single oral dose. Twenty-four hours after the DMAA injection, there was increased formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum and urine and a higher number of DNA strand breaks in peripheral blood cells. These increased levels were concomitant with increasing dose concentrations of DMAA in both strains of mice and they were significantly higher in MT-I/II null mice than in wild-type mice. Furthermore, the induction of apoptotic cells in the urinary bladder epithelium of MT-I/II null mice was significantly higher than in dose-matched wild-type mice exposed to DMAA. On the other hand, in both liver and in the alveolar and bronchial areas of the lung, the extent of DMAA-induced apoptosis was not different between wild-type and MT-I/II null mice and was increased in both strains. In addition, the concentration of hepatic MT in wild-type mice increased in a DMAA dose-dependent manner but was undetectable in MT-I/II null mice and could not subsequently be induced by DMAA. In conclusion, DMAA exposure causes oxidative stress, DNA damage and specific induction of apoptosis in target organs of arsenic carcinogenesis, which may be attributable to the mechanism(s) of arsenic-induced carcinogenesis in rodents. MT exhibited some protective roles during DNA damage presumably by acting as an antioxidant.

Related Articles

Journal Cover

August 2004
Volume 25 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Jia G, Sone H, Nishimura N, Satoh M and Tohyama C: Metallothionein (I/II) suppresses genotoxicity caused by dimethylarsinic acid. Int J Oncol 25: 325-333, 2004.
APA
Jia, G., Sone, H., Nishimura, N., Satoh, M., & Tohyama, C. (2004). Metallothionein (I/II) suppresses genotoxicity caused by dimethylarsinic acid. International Journal of Oncology, 25, 325-333. https://doi.org/10.3892/ijo.25.2.325
MLA
Jia, G., Sone, H., Nishimura, N., Satoh, M., Tohyama, C."Metallothionein (I/II) suppresses genotoxicity caused by dimethylarsinic acid". International Journal of Oncology 25.2 (2004): 325-333.
Chicago
Jia, G., Sone, H., Nishimura, N., Satoh, M., Tohyama, C."Metallothionein (I/II) suppresses genotoxicity caused by dimethylarsinic acid". International Journal of Oncology 25, no. 2 (2004): 325-333. https://doi.org/10.3892/ijo.25.2.325