Potassium bromate (KBrO 3) is a rodent carcinogen and a nephro- and neurotoxicant in humans. KBrO3 is used in cosmetics and food products and is a by-product of water disinfection by ozonization. KBrO3 is carcinogenic in the rat kidney, thyroid, and mesothelium and is a renal carcinogen in the male mouse. The present study was designed to investigate the relationship of time and dose to bromate-induced tumors in male Fischer 344 (F344) rats and to provide some insight into the development of these tumors. KBrO 3 was dissolved in drinking water at nominal concentrations of 0, 0.02, 0.1, 0.2, and 0.4 g/L and administered to male F344 rats as the sole water source for 12, 26, 52, 78, or 100 wk. Renal cell tumors were present after 52 wk of treatment only in the high-dose group. Mesotheliomas developed after 52 wk of treatment on the tunica vaginalis. Mesotheliomas were present at sites other than the testicle after 78 wk of treatment, indicating that their origin was the testicular tunic. Thyroid follicular tumors were present as early as 26 wk in 1 rat each from the 0.1- and 0.2-g/L groups. The present study can be used as a basis for the determination of dose-time relationships of tumor development for a better understanding of KBrO3-induced cancer.
Anderson FA (1994). Final report on the safety assessment of sodium bromate and potassium bromate. J. Am. Coll. Toxicol. 13: 400-414.
2.
Burry A. (1978). Pathology of analgesic nephropathy: Australian experience. Kidney Int. 13: 34-40.
3.
Cavanagh JE, Weinberg HS, Gold A., Sangalah R., Marbury D., Glase WH, Collette TW, Richardson SD, and Thruston AD (1992). Ozonation byproducts: Identification of bromohydrins from the ozonation of natural waters with enhanced bromide levels. Environ. Sci. Technol. 26: 1658-1662.
4.
Corless CL, Kibel AS, Iliopoulos O., and Kaelin WG (1997). Immunostaining of the von Hippel-Lindau gene product in normal and neoplastic human tissues. Hum. Pathol. 28: 459-464.
5.
Crosby LM, Morgan KT, and DeAngelo AB (1998). Potassium bromate-induced mesothelioma localizes to the mesorchium of the tunica vaginalis testis of the F344 rat. Toxicol. Sci. 42(suppl. 1): 72.
6.
DeAngelo AB, George MH, Kilburn SR, Moore TM, and Wolf DC (1998). Carcinogenicity of potassium bromate administered in the drinking water to male B6C3F1 mice and F344/N rats. Toxicol. Pathol. 26: 587-594.
7.
Fleming S. (1997). Genetics of renal tumours. Cancer Metastasis Rev. 16: 127-140.
8.
Hall WC ( 1990). Peritoneum, retroperitoneum, mesentery, and abdominal cavity. In: Pathology of the Fischer Rat, GA Boorman, SL Eustis , MR Elwell, CA Montgomery, and WF MacKenzie (eds). Academic Press, Inc., San Diego, pp. 63-69.
9.
Hardisty JF and Boorman GA (1990). Thyroid gland. In: Pathology of the Fischer Rat, GA Boorman, SL Eustis, MR Elwell , CA Montgomery, and WF MacKenzie (eds). Academic Press, Inc., San Diego, pp. 519-534.
10.
International Agency for Research on Cancer (1986). Potassium bromate. IARC Monogr. Eval. Carcinog. Risks Hum. 40: 207-220.
11.
Ishidate M. , Sofuni T., Yoshikawa K., Hayashi M., Nohmi T., Sawada M., and Matsuoka A. (1984). Primary mutagenicity screening of food additives currently used in Japan. Food Chem. Toxicol. 22: 623-636.
12.
Kenck C., Whilhelm M., Bugert P., Staehler G., and Kovacs G. (1996). Mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinomas. J. Pathol. 179: 157-161.
13.
Kurata Y., Diwan BA, and Ward JM (1992). Lack of renal tumour-initiating activity of a single dose of potassium bromate, a genotoxic renal carcinogen in male F344/NCr rats. Food. Chem. Toxicol. 30: 251-259.
14.
Kurokawa Y. , Aoki S., Matsushima Y., Takamura N., Imazawa T., and Hayashi Y. (1986). Dose-response studies on the carcinogenicity of potassium bromate in F344 rats after long-term oral administration. J. Natl. Cancer Inst. 77: 977-982.
15.
Kurokawa Y. , Hayashi Y., Maekawa A., Takahashi M., and Kokubo T. (1982). Induction of renal cell tumors in F-344 rats by oral administration of potassium bromate, a food additive . Gann73: 335-338.
16.
Kurokawa Y. , Hayashi Y., Maekawa A., Takahashi M., Kokubo T., and Odashima S. (1983). Carcinogenicity of potassium bromate administered orally to F344 rats. J. Natl. Cancer Inst. 71: 965-972.
17.
Kurokawa Y. , Maekawa A., Takahashi M., and Hayashi Y. (1990). Toxicity and carcinogenicity of potassium bromate-a new renal carcinogen. Environ. Health Perspect. 87: 309-335.
18.
Kurokawa Y. , Matsushima Y., Takamure N., Imazawa T., and Hayashi Y. (1987). Relationship between the duration of treatment and the incidence of renal cell tumors in male F344 rats administered potassium bromate. Jpn. J. Cancer Res. 78: 358-364.
19.
Kurokawa Y. , Takamura N., Matsuoka C., Imazawa T., Matsushima Y., Onodera H., and Hayashi Y. (1987). Comparative studies on lipid peroxidation in the kidney of rats, mice, and hamsters and on the effect of cysteine, glutathione, and diethyl maleate treatment on mortality and nephrotoxicity after administration of potassium bromate . J. Am. Coll. Toxicol . 6: 489-501.
20.
Kurokawa Y. , Takamura N., Matsushima Y., Imazawa T., and Hayashi Y. (1984). Studies on the promoting and complete carcinogenic activities of some oxidizing chemicals in skin carcinogenesis . Cancer Lett. 24: 299-304.
21.
Kurokawa Y. , Takayama S., Konishi Y., Hiasa Y., Asahina S., Takahashi M., Maekawa A., and Hayashi Y. (1986). Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan. Environ. Health Perspect . 69: 221-235.
22.
Matsushima Y., Takamura N., Imazawa T., Kurokawa Y., and Hayashi Y. (1986). Lack of carcinogenicity of potassium bromate after subcutaneous injection of newborn mice and newborn rats. Sci. Rep. Res. Inst. Tohoku Univ. 33: 22-26.
23.
Montgomery CA and Seely JC (1990). Kidney. In: Pathology of the Fischer Rat, GA Boorman, SL Eustis, MR Elwell , CA Montgomery , and WF MacKenzie (eds). Academic Press, Inc., San Diego, pp. 140-142.
24.
Sai K., Takagi A., Umemura T., Hasegawa R., and Kurokawa Y. (1991). Relation of 8-hydroxydeoxyguanosine formation in rat kidney to lipid peroxidation, glutathione level and relative organ weight after a single administration of potassium bromate. Jpn. J. Cancer Res. 82: 165-169.
25.
Sai K., Uchiyama S., Ohno Y., Hasegawa R., and Kurokawa Y. (1992). Generation of active oxygen species in vitro by the interaction of potassium bromate with rat kidney cell. Carcinogenesis13: 333-339.
26.
Sai K., Umemura T., Takagi A., Hasegawa R., and Kurokawa Y. (1992). The protective role of glutathione, cysteine and vitamin C against oxidative DNA damage induced in rat kidney by potassium bromate. Jpn. J. Cancer Res. 83: 45-51.
27.
Thomas GA and Williams D. (1994). Changes in structure and function of the thyroid follicular cell. In: Patholobiology of the Aging Rat, Vol. 2, U Mohr, DL Dungworth, CC Capen (eds). ILSI Press, Washington, D.C., pp. 277-280.
28.
Umemura T., Takagi A., Sai K., Hasegawa R., and Kurokawa Y. (1998). Oxidative DNA damage and cell proliferation in kidneys of male and female rats during 13-weeks exposure to potassium bromate (KBrO3). Arch. Toxicol. 72: 264-269.
29.
Urakami S., Tokuzen R., Tsuda H., Igawa M., and Hino O. (1997). Somatic mutation of the tuberous sclerosis (Tsc2) tumor suppressor gene in chemically induced rat renal carcinoma cell. J. Urol. 158: 275-278.
30.
Walker C. (1998). Molecular genetics of renal carcinogenesis. Toxicol. Pathol. 26: 113-120.
