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环境病理学,毒理学和肿瘤学期刊
影响因子: 1.625 5年影响因子: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.v27.i1.50
pages 43-52

Tissue Levels of Arsenicals and Skin Tumor Response Following Administration of Monomethylarsonous Acid and Arsenite to K6/ODC Mice

Yan Chen
ODC Mouse Group Inc., 1209 Childs Ave, Drexel Hill, PA 19026, USA
Tom O'Brien
ODC Mouse Group Inc., 1209 Childs Ave, Drexel Hill, PA 19026, USA
Luz Maria Del Razo
Toxicology Department, CINVESTAV-IPN, Mexico City, Mexico
David J. Thomas
Environmental Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711
Kirk T. Kitchin
Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711

ABSTRACT

The effects of monomethylarsonous acid (MMA[III]) and arsenite, administered in drinking water on tissue levels of arsenicals, cytogenetics, and mouse skin tumorigenicity were determined. A low-methionine diet modified the pattern of arsenical tissue concentrations and decreased the tissue arsenical concentrations, particularly in kidney and urinary bladder, less so in liver, and had little effect in the lungs. In mice given 75 ppm arsenite and a low-methionine diet, the urinary bladder tissue levels were only 29%, 26%, and 38% of the inorganic arsenic (iAs), MMA, and dimethylarsinic acid (DMA) concentrations found in mice eating the control diet. In K6/ODC transgenic mice that consumed a normal diet (Purina 5002), a 26-week drinking water exposure to 10 ppm arsenite resulted in 5% of the treated animals having squamous skin tumors. Exposure to 10, 50, 75, or 150 ppm MMA(III) caused 5%, 6.7%, 5%, or 0% tumor-bearing animals. A low-methionine diet did not markedly change the incidence of skin tumors—10 ppm arsenite led to 10% tumors. With a low-methionine diet, 10 and 50 ppm, MMA(III) caused 5% and 6.7% tumor-bearing animals. In comparing the frequency of tumors in the concurrent control groups (1/70, 1.4%) with the frequency of tumors in the pooled arsenical-treated responsive groups (8/122, 6.6%), there is an excess of 6 mouse skin tumors observed in the pooled arsenical-responsive treatment groups compared to the expected number of tumors based on frequency of tumors observed in concurrent control mice. In summary, studies with MMA(III) and arsenite-treated K6/ODC transgenic mice showed (1) a low-methionine diet substantially altered mouse tissue arsenical levels and (2) numerically elevated incidence of mouse skin tumors following arsenical exposures.


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