Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1997 Dec;88(12):1149-54.
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

H Wanibuchi  1 , T Hori, V Meenakshi, T Ichihara, S Yamamoto, Y Yano, S Otani, D Nakae, Y Konishi, S Fukushima
Affiliations

Promotion of rat hepatocarcinogenesis by dimethylarsinic acid: association with elevated ornithine decarboxylase activity and formation of 8-hydroxydeoxyguanosine in the liver

H Wanibuchi et al. Jpn J Cancer Res. 1997 Dec.

Abstract

Arsenicals are epidemiologically 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 preneoplastic 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.

PubMed Disclaimer

References

    1. ) IARC. Arsenic and arsenic compounds . In “ Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol. 23: Some Metals and Metallic Compounds ” pp. 39 – 141 ( 1980. ). IARC; , Lyon . - PubMed
    1. ) IARC. “ Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol. 1–40, Suppl. 7: Overall Evaluation of the Carcinogenicity: An Updating of IARC Monographs ” pp. 100 – 106 ( 1987. ). IARC; , Lyon .
    1. ) Risk Assessment Forum . “ Special Report on Ingested Inorganic Arsenic: Skin Cancer; Nutritional Essentiality ” ( 1988. ). US Environmental Protection Agency; , Washington, DC .
    1. ) Chen , C.‐J. , Chuang , Y.‐C. , Lin , T.‐M. and Wu , H.‐Y.Malignant neoplasms among residents of a blackfoot disease endemic area in Taiwan: high‐arsenic artesian well water and cancers . Cancer Res. , 45 , 5895 – 5899 ( 1985. ). - PubMed
    1. ) Chen , C.‐J. , Chuang , Y.‐C. , You , S.‐L. , Lin , T.‐M. and Wu , H.‐Y.A retrospective study on malignant neoplasms of bladder, lung and liver in blackfoot disease endemic area in Taiwan . Br. J. Cancer , 53 , 399 – 405 ( 1986. ). - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources