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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1997 Dec;88(12):1149–1154. doi: 10.1111/j.1349-7006.1997.tb00343.x

Promotion of Rat Hepatocarcinogenesis by Dimethylarsinic Acid: Association with Elevated Ornithine Decarboxylase Activity and Formation of 8‐Hydroxydeoxyguanosine in the Liver

Hideki Wanibuchi 1,✉, Takaaki Hori 1, Vijayaraghavan Meenakshi 1, Toshio Ichihara 1, Shinji Yamamoto 1, Yoshihisa Yano 2, Shuzo Otani 2, Dai Nakae 3, Yoichi Konishi 3, Shoji Fukushima 1
PMCID: PMC5921341  PMID: 9473732

Abstract

Arsenicals are epidemiologicaUy significant chemicals in relation to induction of liver cancer in man. In the present study, we investigated the dose‐dependent promotion potential of dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenicals in mammals, in a rat liver carcinogenesis model. In experiment 1, glutathione‐S‐transferase placental form (GST‐P)‐positive foci, putative preneoplas‐tic lesions, were employed as endpoints of a liver medium‐term bioassay for carcinogens (Ito test). Starting 2 weeks after initiation with diethylnitrosamine, male F344 rats were treated with 0, 25, 50 or 100 ppm of DMAA in the drinking water for 6 weeks. All animals underwent two‐thirds partial hepatectomy at week 3 after initiation. Examination of liver sections after termination at 8 weeks revealed dose‐dependent increases in the numbers and areas of GST‐P‐positive foci in DMAA‐treated rats as compared with controls. In experiment 2, ornithine decarboxylase activity, which is a biomarker of cell proliferation, was found to be significantly increased in the livers of rats treated with DMAA. In experiment 3, formation of 8‐hydroxydeoxyguanosine, which is a marker of oxygen radical‐mediated DNA damage, was significantly increased after administration of DMAA. These results indicate that DMAA has the potential to promote rat liver carcinogenesis, possibly via a mechanism involving stimulation of cell proliferation and DNA damage caused by oxygen radicals

Keywords: Dimethylarsinic acid, 8‐Hydroxydeoxyguanosine, Ornithine decarboxylase, Rat hepatocarcinogenesis

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