The role of trivalent dimethylated arsenic in dimethylarsinic acid-promoted skin and lung tumorigenesis in mice: tumor-promoting action through the induction of oxidative stress.

Abstract

We investigated the relationship between lung- and skin-tumor promotion and oxidative stress caused by administration of dimethylarsinic acid (DMA(V)) in mice. The incidence of lung tumors induced by lung tumor initiator (4NQO) and DMA(V) were, as well as 8-oxo-2'-deoxyguanosine (8-oxodG), suppressed by cotreatment with (-)epigallocatechin gallate (EGCG). When mice were topically treated with trivalent dimethylated arsenic (DMA(III)), a further reductive metabolite of DMA(V), not only an increase in skin tumors but also an elevation of 8-oxodG in epidermis were observed. These results suggest that tumor promotion due to DMA(V) administration is mediated by DMA(III) through the induction of oxidative stress.

• Authors: Mutsumi Mizoi, Fumiyo Takabayashi, Masayuki Nakano, Yan An, Yuko Sagesaka, Koichi Kato, Shoji Okada, Kenzo Yamanaka
• Journal: Toxicology letters (Toxicol Lett) Vol. 158 Issue 2 Pg. 87-94 (Aug 14 2005) ISSN: 0378-4274 [Print] Netherlands
• PMID: 16039397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Herbicides
• dimethylarsinous acid
• 8-Hydroxy-2'-Deoxyguanosine
• Cacodylic Acid
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Adenoma (chemically induced, metabolism)
• Administration, Topical
• Animals
• Cacodylic Acid (analogs & derivatives, metabolism, toxicity)
• Carcinogenicity Tests
• Carcinogens (metabolism, toxicity)
• Deoxyguanosine (analogs & derivatives, metabolism)
• Female
• Herbicides (metabolism, toxicity)
• Lung Neoplasms (chemically induced, metabolism)
• Male
• Mice
• Mice, Hairless
• Oxidative Stress (drug effects)
• Skin Neoplasms (chemically induced, metabolism)