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Effect of Sodium Arsenite Dose Administered in the Drinking Water on the Urinary Bladder Epithelium of Female Arsenic (+3 oxidation state) Methyltransferase Knockout Mice
Citation:
Yokohira, M., L. L. Arnold, K. L. Pennington, S. Shugo, S. Kakiuchi-Kiyota, S. N. Cohen, AND D. J. THOMAS. Effect of Sodium Arsenite Dose Administered in the Drinking Water on the Urinary Bladder Epithelium of Female Arsenic (+3 oxidation state) Methyltransferase Knockout Mice. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 121(2):257-266, (2011).
Impact/Purpose:
In the present study, we showed that the cytotoxic and proliferative effects of arsenite on the urothelium are dose dependent.
Description:
The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, we evaluated whether the As3mt null genotype in mice modified cytotoxic and proliferative effects in urinary bladders of wild type mice after inorganic arsenic exposure. Female As3mt knockout (KG) mice treated with diet containing 100 or 150 ppm arsenic as arsenite showed systemic toxicity and significant effects on the urothelium. In the present study, we showed that the cytotoxic and proliferative effects of arsenite on the urothelium are dose dependent. Female wild type C57BL/6 mice and As3mt KG mice were divided into 5 groups each (n=7) with free access to drinking water containing 0, 1, 10, 25 or 50 ppm arsenic as arsenite for 4 weeks. At sacrifice, urinary bladders of both As3mt KG and wild type mice showed hyperplasia by light microscopy, however the hyperplasia was more severe in the As3mt KG mice. A no effect level was identified at 1 ppm arsenic. In As3mt KG mice, numerous cytoplasmic and nuclear granules were present in all urothelial layers and were larger and more abundant than the granules in wild type mice. In As3mt KG mice, livers showed mild acute inflammation and kidneys showed hydronephrosis. Thus, diminished arsenic As3mt KG mice exacerbates the effects of arsenite on the bladder epithelium.
