Skin and Liver Cancer induced by monomethylarsonous acid (MMAIII) in mice

Krishnamohan, Manonmanii, Shareef, Mohammed M., Moore, Michael R., Seawright, Alan A., Carey, David J., Ahmed, Mansoor M. and Ng, Jack C. (2006). Skin and Liver Cancer induced by monomethylarsonous acid (MMAIII) in mice. In: J. Kniewald, Toxicology Letters. Abstracts of the EUROTOX 2006/6 CTDC Congress - 43rd Congress of the European Societies of Toxicology & 6th Congress of Toxicology in Developing Countries. EUROTOX 2006/6 CTDC Congress - 43rd Congress of the European Societies of Toxicology & 6th Congress of Toxicology in Developing Countries, Cavtat, Croatia, (259-259). 20-24 September 2006. doi:10.1016/j.toxlet.2006.07.198


Author Krishnamohan, Manonmanii
Shareef, Mohammed M.
Moore, Michael R.
Seawright, Alan A.
Carey, David J.
Ahmed, Mansoor M.
Ng, Jack C.
Title of paper Skin and Liver Cancer induced by monomethylarsonous acid (MMAIII) in mice
Formatted title
Skin and liver cancer induced by monomethylarsonous acid (MMAIII) in mice
Conference name EUROTOX 2006/6 CTDC Congress - 43rd Congress of the European Societies of Toxicology & 6th Congress of Toxicology in Developing Countries
Conference location Cavtat, Croatia
Conference dates 20-24 September 2006
Proceedings title Toxicology Letters. Abstracts of the EUROTOX 2006/6 CTDC Congress - 43rd Congress of the European Societies of Toxicology & 6th Congress of Toxicology in Developing Countries   Check publisher's open access policy
Journal name Toxicology Letters   Check publisher's open access policy
Place of Publication Ireland
Publisher Elsevier
Publication Year 2006
DOI 10.1016/j.toxlet.2006.07.198
ISSN 0378-4274
Editor J. Kniewald
Volume 164
Issue Supp. 1
Start page 259
End page 259
Total pages 1
Language eng
Formatted Abstract/Summary
Although arsenic is toxic and a proven carcinogen, the mechanism underlying carcinogenesis is unknown. Until recently the metabolism of arsenic was thought to be a detoxification process. MMAIII is a toxic intermediate of arsenic metabolism. Recent studies show that MMAIII is more cytotoxic and genotoxic than AsIII or AsV. Our aim was to develop an animal model to study the role of MMAIII in arsenic carcinogenesis and in particular to study the development of skin cancer, the predominant presenting feature in humans.

Female C57BL/6J mice were given drinking water containing 0 μg/L and 500 μg/L arsenic as MMAIII ad libitum for 2 years. Five animals from each group were sacrificed at various times up to 24 months for arsenic and biomarker measurements. HPLC–ICPMS was used to assess excretion of As species. DMAV was the major metabolite which showed a significant dose-dependent increase over 2 years of exposure.

An excess of tumors were observed in the MMAIII-treated animals around 18 months. MMAIII treatment resulted in firstly, dermatitis which progressed to trichoepithelioma. There was also an excess of liver cancer. Genome-wide expression profiling of the liver tumors induced by MMAIII by Affymetrix (Mouse genome 430 2.0Array) system for 45,000 probe sets, indicated the disruption of signaling pathways. The components mediating the outcome were different in treatment modalities with the same end result of increase in the expression of Bcl2 a prosurvival gene.

Our results show MMAIII is carcinogenic in female C57BL/6J mice and supports the contention that methylation is a toxic process, not a detoxification pathway. MMAIII derived metabolically from inorganic arsenic is likely to be the proximal carcinogen.

Subjects CX
321299 Public Health and Health Services not elsewhere classified
730210 Environmental health
Q-Index Code CX
Additional Notes Scopus EID incorporates the entire proceedings from pages S3-324.

 
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Created: Wed, 15 Aug 2007, 10:58:30 EST