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MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS
Citation:
McDorman, K AND D C. Wolf. MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS. Presented at Society of Toxicologic Pathologists, Orlando, Florida, June 24-28, 2001.
Description:
MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS
Epidemiological studies have shown a positive association between chronic exposure to chlorinated drinking water and human cancer, particularly of the urinary bladder. MX (3- chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone) is a disinfection by-product (DBP) and a multisite carcinogen in both male and female rats. MX poses a significant public health concern because it is the most potent mutagen present in chlorinated drinking water. A study was designed to investigate the effects of four individual and a mixture of these D BPs in the Eker rat model of hereditary renal cell carcinoma. Male and female Eker rats were exposed via drinking water to individual or a mixture of D BPs until 6 or 12 months of age. MX, potassium bromate, chloroform, and bromodichloromethane were administered at low doses of 0.005, 0.02, 0.4 and 0.07 g/L, respectively and high doses of 0.07, 0.4, 1.8 and 0.7 g/L, respectively. Low and high dose mixture solutions were comprised of all four chemicals at either low doses or high doses, respectively. Bromodeoxyuridine (BrdU) was administered via drinking water for 4 days prior to necropsy. Exposure to MX caused multifocal epithelial hyperplasia and individual transitional cell hypertrophy with marked karyomegaly in the urinary bladder of male and female Eker rats at both time points. This lesion was not present in control animals and only rarely observed in animals exposed to the DBP mixture. An increase in cell proliferation was present in the urinary bladder epithelium of rats exposed to the high dose MX. Epithelial proliferation was greater in female rats compared to male rats. These data indicate that chronic exposure to MX at high doses can cause hyperplasia with enhanced cell proliferation in the rat urinary bladder, but this effect is diminished in a mixture.
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