Diphenylarsinic acid (DPAA), a degradation product of chemical warfare agents, is still remained in groundwater and soil in some regions of Japan due to illegal dumping after World War II. Health concern has been growing about the toxicity and carcinogenicity of DPAA since dysfunction of the central nervous system was reported in residents chronically exposed to DPAA in Kamisu-machi, Ibaraki Prefecture, Japan. The purpose of the present study is to evaluate the modifying effects of DPAA on rat hepatocarcinogenesis induced by diethylnitrosamine (DEN) using a medium-term rat liver carcinogenesis assay (Ito test). At the beginning of the study, rats in groups 1-4 were given a single intraperitoneal injection of DEN to initiate hepatocarcinogenesis. Rats in groups 5 and 6 were given saline vehicle alone. After 2 weeks, they were given DPAA in the drinking water for 6 weeks as follows: groups 1-4, 0, 5, 10, 20 ppm, respectively; groups 5 and 6, 0, 20 ppm, respectively. All animals were subjected to two-thirds partial hepatectomy at the end of week 3. At the end of week 8, administration of 20 ppm DPAA (group 4) significantly increased the numbers and areas of glutathione S-transferase placental form positive foci, which are preneoplatic lesions in the rat liver, compared to DEN alone group (group 1), while DPAA at doses of 5 and 10 ppm had not effects. There were no significant changes in formation of 8-hydroxy-2'-deoxyguanosine in liver DNA among groups. There results indicated that DPAA exerts promotion effects on hepatocarcinogenesis in rats and that oxidative DNA damage is not involved in its carcinogenic effects.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA