Abstract 4364: Mechanism of promotion effect of diphenylarsenic acid on rat liver carcinogenesis

Abstract

Abstract Diphenylarsinic acid (DPAA) is an enviromental degradation of product of diphenylarsine chloride or diphenylarsine cyanide, which were chemical warfare agents produced by Japan during the World War II. DPAA is now considered a dangerous environmental pollution in Kamisu, Japan, where it is suspected of inducing health effect that include articulation disorders, involuntary movements, and sleep disorders. We previously showed that GST-P (Glutathione S-transferase P) positive foci which is precancerous condition increased the number and the area at DPAA 20 ppm but not at below on rat liver carcinogenesis in medium-term bioassay (Ito test), suggesting that DPAA had promotion activities. However, the mechanism of its promotion activities is unclear. The purpose of present study is to clarify the mechanism of DPAA-induced promotion activity in rat liver carcinogenesis. We found that DPAA at 20 ppm but not at below increased significantly in oxidative DNA damage, mRNA expression of CYP1B1, cyclin D1, and c-Myc, and protein level and transcriptional activity of AhR (Arylhydrocarbon receptor) which is implicated in most of the biological responses to the environmental contaminant (e.g. TCDD). Proteome analysis showed that 69 proteins were differentially up or down-regulated in DEN-DPAA 20ppm group compared with DEN alone including 18 proteins of AhR pathway. These results suggested that activity of AhR pathway and oxidative DNA damage on rat liver carcinogenesis involved in promotion activity of DPAA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4364.