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.