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Toxicologic Pathology
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Induction of Transitional Cell Hyperplasia in the Urinary Bladder and Aberrant Crypt Foci in the Colon of Rats Treated with Individual and a Mixture of Drinking Water Disinfection By-Products

Kevin S. Mcdorman

Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599

Sundeep Chandra

Experimental Pathology Laboratories, Inc., Research Triangle Park, North Carolina 27709

Michelle J. Hooth

Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory (NHEERL), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Susan D. Hester

Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory (NHEERL), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Robert Schoonhoven

Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599

Douglas C. Wolf

Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599, wolf.doug{at}epamail.epa.gov, Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory (NHEERL), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Cancer of the urinary bladder and colon are significant human health concerns. Epidemiological studies have suggested a correlation between these cancers and the chronic consumption of chlorinated surface water containing disinfection by-products (DBPs). The present study was designed to determine if exposure to DBPs would cause preneoplastic or neoplastic lesions in the urinary bladder and colon of rats, and what effect a mixture of DBPs would have on these lesions. Male and female Eker rats were treated via drinking water with low and high concentrations of potassium bromate, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), chloroform, or bromodichloromethane individually or in a mixture for 10 months. The urinary bladders and colons were examined for the presence of preneoplastic lesions. Cell proliferation in the urothelium was examined using immunohistochemical staining for bromodeoxyuridine. Aberrant crypt foci (ACF), as well as the number of individual crypts in each ACF, were identified and counted microscopically after staining with 0.2% methylene blue. Colon crypt cell proliferation and mitotic index were determined using immunohistochemical staining for proliferating cell nuclear antigen. Labeling indexes for the urinary bladder and colon were calculated based on the percentage of positively labeled cells. Treatment with the high dose of MX caused transitional epithelial hyperplasia and cell proliferation in the rat urinary bladder, and this effect was diminished in the high dose mixture animals. Treatment with 4 individual DBPs, as well as a mixture of them, caused the development of ACF, the putative preneoplastic lesion of colon cancer.

Key Words: Rat • urinary bladder • colon • aberrant crypt foci • water • disinfection by-products • cell proliferation.

References

  • Bird RP, Pretlow TP (1992). Correspondence re: Giovanna Caderni et al., Effect of dietary carbohydrates on the growth of dysplastic crypt foci in the colon of rats treated with 1,2-dimethylhydrazine. In: Cancer Res 51: 3721—3725, 1991. Cancer Res 52: 4291—4292.[Web of Science]
  • Bird RP (1995). Role of aberrant crypt foci in understanding the pathogenesis of colon cancer. Cancer Lett 93: 55—71.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Brauers A., Jakse G. (2000). Epidemiology and biology of human urinary bladder cancer. J Cancer Res Clin Oncol 126: 575—583.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Brunborg G., Holme JA, Soderlund EJ, Hongslo JK, Vartiainen T., Lotjonen S., Becher G. (1991). Genotoxic effects of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in mammalian cells in vitro and in rats in vivo. Mutat Res 260: 55—64.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bull RJ, Birnbaum LS, Cantor KP, Rose JB, Butterworth BE, Pegram R., Tuomisto J. (1995). Water chlorination: Essential process or cancer hazard? Fundam Appl Toxicol 28: 155—166.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Butterworth BE (1990). Consideration of both genotoxic and nongenotoxic mechanisms in predicting carcinogenic potential. Mutat Res 239: 117—132.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cantor KP, Hoover R., Hartge P., Mason TJ, Silverman DT, Altman R., Austin DF, Child MA, Key CR, Marrett LD, et al. (1987). Bladder cancer, drinking water source, and tap water consumption: A case-control study. J Natl Cancer Inst 79: 1269—1279.[Web of Science][Medline] [Order article via Infotrieve]
  • Cantor KP, Lynch CF, Hildesheim ME, Dosemeci M., Lubin J., Alavanja M., Craun G. (1998). Drinking water source and chlorination byproducts. I. Risk of bladder cancer. Epidemiology 9: 21—28.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Chen TX, Wanibuchi H., Wei M., Morimura K., Yamamoto S., Hayashi S., Fukushima S. (1999). Concentration dependent promoting effects of sodium L-ascorbate with the same total dose in a rat two-stage urinary bladder carcinogenesis. Cancer Lett 146: 67—71.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cohen SM (1983). Promotion in urinary bladder carcinogenesis. Environ Health Perspect 50: 51—59.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cohen SM, Johansson SL (1992). Epidemiology and etiology of bladder cancer. Urol Clin North Am 19: 421—428.[Web of Science][Medline] [Order article via Infotrieve]
  • Crawford JM (1999). The gastrointestinal tract. In: Robbins' Pathologic Basis of Disease, Cotran RS, Kumar V, Collins T (eds). WB Saunders Co, Philadelphia, PA, pp 831—835.
  • DeAngelo AB, George JH (1999). The induction of aberrant crypt foci (ACF) in the colons of rodents administered trihalomethanes (THMs) in the drinking water. Toxicol Sci 48: 343.
  • DeMarini DM, Landi S., Ohe T., Shaughnessy DT, Franzen R., Richard AM (2000). Mutation spectra in Salmonella of analogues of MX: Implications of chemical structure for mutational mechanisms. Mutat Res 453: 51—65.[Web of Science][Medline] [Order article via Infotrieve]
  • Doyle TJ, Zheng W., Cerhan JR, Hong CP, Sellers TA, Kushi LH, Folsom AR (1997). The association of drinking water source and chlorination byproducts with cancer incidence among postmenopausal women in Iowa: A prospective cohort study. Am J Public Health 87: 1168—1176.[Abstract/Free Full Text]
  • Dunnick JK, Eustis SL, Lilja HS (1987). Bromodichloromethane, a trihalomethane that produces neoplasms in rodents. Cancer Res 47: 5189— 5193.[Abstract/Free Full Text]
  • Eldridge SR, Tilbury LF, Goldsworthy TL, Butterworth BE (1990). Measurement of chemically induced cell proliferation in rodent liver and kidney: A comparison of 5-bromo-2'-deoxyuridine and (3H)thymidine administered by injection or osmotic pump. Carcinogenesis 11: 2245—2251.[Abstract/Free Full Text]
  • Fenoglio-Preiser CM, Noffsinger A. (1999). Aberrant crypt foci: A review. Toxicol Pathol 27: 632—642.[Free Full Text]
  • Franzen R., Tanabe K., Morita M. (1998). Isolation of a MX-guanosine adduct formed at physiological conditions. Chemosphere 36: 2803—2808.[Medline] [Order article via Infotrieve]
  • Fukushima S., Murasaki G., Hirose M., Nakanishi K., Hasegawa R., Ito N. (1982). Histopathological analysis of preneoplastic changes during N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats. Acta Pathol Jpn 32: 243—250.[Medline] [Order article via Infotrieve]
  • Ghadirian P., Maisonneuve P., Perret C., Lacroix A., Boyle P. (1998). Epidemiology of sociodemographic characteristics, lifestyle, medical history, and colon cancer: A case-control study among French Canadians in Montreal. Cancer Detect Prev 22: 396—404.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ghia M., Mereto E., Cavanna M., Brambilla G. (1996). Inhibition of the development of rat liver preneoplastic lesions by verapamil and dexverapamil. Anticancer Res 16: 1739—1741.[Web of Science][Medline] [Order article via Infotrieve]
  • Herrero-Jimenez P., Thilly G., Southam PJ, Tomita-Mitchell A., Morgenthaler S., Furth EE, Thilly WG (1998). Mutation, cell kinetics, and subpopulations at risk for colon cancer in the United States. Mutat Res 400: 553— 578.[Web of Science][Medline] [Order article via Infotrieve]
  • Hildesheim ME, Cantor KP, Lynch CF, Dosemeci M., Lubin J., Alavanja M., Craun G. (1998). Drinking water source and chlorination byproducts. II. Risk of colon and rectal cancers. Epidemiology 9: 29—35.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hooth MJ, McDorman KS, Hester SD, George MH, Brooks LR, Swank AE, Wolf DC ( 2002). The carcinogenic response of Tsc2 mutant Long-Evans (Eker) rats to a mixture of drinking water disinfection by-products was less than additive. Toxicol Sci 69: 322—331.[Abstract/Free Full Text]
  • Johansson SL, Cohen SM (1997). Epidemiology and etiology of bladder cancer. Semin Surg Oncol 13: 291—298.[CrossRef]
  • Kim TW, Porter KL, Foley JF, Maronpot RR, Smart RC (1997). Evidence that mirex promotes a unique population of epidermal cells that cannot be distinguished by their mutant Ha-ras genotype. Mol Carcinog 20: 115—124.[Medline] [Order article via Infotrieve]
  • King WD, Marrett LD, Woolcott CG (2000). Case-control study of colon and rectal cancers and chlorination by-products in treated water. Cancer Epidemiol Biomarkers Prev 9: 813—818.[Abstract/Free Full Text]
  • Komulainen H., Kosma VM, Vaittinen SL, Vartiainen T., Kaliste-Korhonen E., Lotjonen S., Tuominen RK, Tuomisto J. (1997). Carcinogenicity of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in the rat. J Natl Cancer Inst 89: 848—856.[Abstract/Free Full Text]
  • Kronberg L., Vartiainen T. (1988). Ames mutagenicity and concentration of the strong mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone and of its geometric isomer E-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid in chlorine-treated tap waters. Mutat Res 206: 177—182.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Le Curieux F., Nesslany F., Munter T., Kronberg L., Marzin D. (1999). Genotoxic activity of chlorohydroxyfuranones in the microscale micronucleus test on mouse lymphoma cells and the unscheduled DNA synthesis assay in rat hepatocytes. Mutagenesis 14: 457—462.[Abstract/Free Full Text]
  • Maskens AP (1976). Histogenesis and growth pattern of 1,2-dimethylhydrazine-induced rat colon adenocarcinoma. Cancer Res 36: 1585—1592.[Abstract/Free Full Text]
  • Meier JR, Blazak WF, Knohl RB (1987). Mutagenic and clastogenic properties of 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone: A potent bacterial mutagen in drinking water. Environ Mol Mutagen 10: 411— 424.[Web of Science][Medline] [Order article via Infotrieve]
  • Meier JR, Knohl RB, Coleman WE, Ringhand HP, Munch JW, Kaylor WH, Streicher RP, Kopfler FC (1987). Studies on the potent bacterial mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone: Aqueous stability, XAD recovery and analytical determination in drinking water and in chlorinated humic acid solutions. Mutat Res 189: 363—373.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Mills CJ, Bull RJ, Cantor KP, Reif J., Hrudey SE, Huston P. (1998). Workshop report. Health risks of drinking water chlorination by-products: Report of an expert working group. Chronic Dis Can 19: 91—102.[Medline] [Order article via Infotrieve]
  • Munter T., Le Curieux F, Sjoholm R., Kronberg L. (1999). Identification of an ethenoformyl adduct formed in the reaction of the potent bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone with guanosine. Chem Res Toxicol 12: 46—52.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Negri E., La Vecchia C (2001). Epidemiology and prevention of bladder cancer. Eur J Cancer Prev 10: 7—14.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Nishikawa A., Furukawa F., Lee IS, Kasahara K., Tanakamaru Z., Nakamura H., Miyauchi M., Kinae N., Hirose M. (1999). Promoting effects of3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone on rat glandular stomach carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine. Cancer Res 59: 2045—2049.[Abstract/Free Full Text]
  • Ochiai M., Nakagama H., Watanabe M., Ishiguro Y., Sugimura T., Nagao M. (1996). Efficient method for rapid induction of aberrant crypt foci in rats with 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine. Jpn J Cancer Res 87: 1029—1033.[CrossRef][Web of Science]
  • Olivo S., Wargovich MJ (1998). Inhibition of aberrant crypt foci by chemopreventive agents. In Vivo 12: 159—166.[Web of Science][Medline] [Order article via Infotrieve]
  • Premoselli F., Sesca E., Chiara M., Binasco V., Tessitore L. (1996). Fasting/ refeeding enhances the crypt multiplicity in rat colon carcinogenesis induced by azoxymethane. Boll Soc Ital Biol Sper 72: 239—245.[Medline] [Order article via Infotrieve]
  • Premoselli F., Sesca E., Binasco V., Franchino C., Tessitore L. (1997). Cell death and cell proliferation contribute to the enhanced growth of foci by fasting in rat medial colon. Boll Soc Ital Biol Sper 73: 71—76.[Medline] [Order article via Infotrieve]
  • Pretlow TP, O'Riordan MA, Somich GA, Amini SB, Pretlow TG (1992). Aberrant crypts correlate with tumor incidence in F344 rats treated with azoxymethane and phytate. Carcinogenesis 13: 1509—1512.[Abstract/Free Full Text]
  • Reddy BS, Narisawa T., Maronpot R., Weisburger JH, Wynder EL (1975). Animal models for the study of dietary factors and cancer of the large bowel. Cancer Res 35: 3421—3426.[Abstract/Free Full Text]
  • Roncucci L. (1992). Early events in human colorectal carcinogenesis. Aberrant crypts and microadenoma. Ital J Gastroenterol 24: 498—501.[Web of Science][Medline] [Order article via Infotrieve]
  • Sasaki YF, Nishidate E., Izumiyama F., Watanabe-Akanuma M., Kinae N., Matsusaka N., Tsuda S. (1997). Detection of in vivo genotoxicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) by the alkaline single cell gel electrophoresis (Comet) assay in multiple mouse organs. Mutat Res 393: 47—53.[Web of Science][Medline] [Order article via Infotrieve]
  • Schafer KA (1998). The cell cycle: A review. Vet Pathol 35: 461—478.[Abstract]
  • Steffensen I., Paulsen JE, Engeset D., Kronberg L., Alexander J. (1999). The drinking water chlorination by-products 3,4-dichloro-5-hydroxy-2(5H)-furanone (mucochloric acid) and 3-chloro-4-(dichloromethyl)-5-hydroxy2(5H)-furanone do not induce preneoplastic or neoplastic intestinal lesions in F344 rats, Balb/cA mice or C57BL/6J-Min mice. Pharm Toxicol 85: 56—64.
  • Takayama T., Katsuki S., Takahashi Y., Ohi M., Nojiri S., Sakamaki S., Kato J., Kogawa K., Miyake H., Niitsu Y. (1998). Aberrant crypt foci of the colon as precursors of adenoma and cancer. N Engl J Med 339: 1277—1284.[Abstract/Free Full Text]
  • Tatematsu M., Fukushima S., Aoki T., Mera Y., Inoue T., Ito N. (1987). Patterns of epithelial proliferation revealed by continuous administration of bromodeoxyuridine during urinary bladder carcinogenesis in rats. Jpn J Cancer Res 78: 879—882.[Web of Science]
  • Tsuda H., Miyata Y., Murasaki G., Kinoshita H., Fukushima S. (1977). Synergistic effect of urinary bladder carcinogenesis in rats treated with N-butyl-n-(4-hydroxybutyl)nitrosamine, N-(4-(5-nitro-2-furyl)-2-thiazolyl)formamide,N-2-fluorenylacetamide, and 3,3'-dichlorobenzidine. Gann 68: 183—192.[Web of Science][Medline] [Order article via Infotrieve]
  • Uchida K., Kado S., Onoue M., Tohyama K. (1997). Relationship between the nature of mucus and crypt multiplicity in aberrant crypt foci in the rat colon. Jpn J Cancer Res 88: 807—814.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Wei M., Wanibuchi H., Yamamoto S., Li W., Fukushima S. (1999). Urinary bladder carcinogenicity of dimethylarsinic acid in male F344 rats. Carcinogenesis 20: 1873—1876.[Abstract/Free Full Text]
  • Wigle DT (1998). Safe drinking water: A public health challenge. Chronic Dis Can 19: 103—107.[Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 31, No. 2, 235-242 (2003)
DOI: 10.1080/01926230390183733
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