| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Although numerous epidemiological findings have indicated that arsenics are associated with increased incidences of lung, skin, liver, and bladder cancers, experimental data from animal models to support the hypothesis of carcinogenic effects are limited. Dimethylarsinic acid (DMA) is a major form of organic arsenic in the environment. In addition, it is a major metabolite of ingested inorganic arsenics in most animals. Male F344/DuCrj rats were administered 12.5, 50, or 200 ppm of DMA in the drinking water for 104 weeks, urinary bladder tumors were observed in 0 of 33,8 of 31, and 12 of 31 animals, respectively. No bladder tumors developed in the controls. These results indicate that DMA is carcinogenic for the rat urinary bladder. Promotion effect of DMA on skin carcinogenesis in K6/ODC transgenic mice were tested. DMA showed promoting effect on skin tumorigenesis in k6/ODC transgenic mice as well as TPA.DMA treatment in NBR rats revealed the elevation of 8-OHdG formation in the kidney . PCNA positive-cells were increased in the rats kidney tissue treated with DMA.Inorganic arsenics (arsenite and arsenate) are metabolized to monomethylarsonic acid (MMA), DMA, and trimethylarsine oxide (TMAO) in most mammals. Promoting effects of sodium arsenite and these related organic arsenics (MMA, DMA, TMAO) in a rat submultiorgan-carcinogenesis test were therefore investigated. With regard to bladder carcinogenesis, DMA most-strongly enhanced the tumor induction, followed in decreasing order by MMA and TMAO, whereas AsBe and NaAsIII did not. The enhancement of bladder carcinogenesis was correlated with production of one unknown urinary metabolite of arsenics. These results revealed that MMA and TMAO have carcinogenic potential, as well as DMA.
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