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. 1986 Nov;69:59–65. doi: 10.1289/ehp.866959

Carcinogenicity of by-products of disinfection in mouse and rat liver.

S L Herren-Freund, M A Pereira
PMCID: PMC1474319  PMID: 2880712

Abstract

By-products of disinfection were tested for initiating and/or promoting activity in rat liver by using the rat liver foci bioassay. The assay uses an increased incidence of gamma-glutamyltranspeptidase-positive foci (GGT foci) as an indicator of carcinogenicity. The by-products of disinfection, including chloramine, halogenated humic acids, halogenated ethanes, halogenated acetonitriles, halogenated methanes, halogenated ethylenes, and N-Cl-piperidine, did not initiate GGT foci, which would indicate that they are not capable of initiating carcinogenesis. Chloroform and halogenated benzenes were tested in this assay for their ability to promote the occurrence of GGT foci and tumors initiated by diethylnitrosamine (DENA). Chloroform (1800 ppm in the drinking water) either had no effect or inhibited the occurrence of GGT foci when administered subsequent to a single dose of DENA. However, when the chloroform was administered in drinking water concurrently with weekly doses of DENA, it enhanced the formation of liver tumors. Of 20 halogenated benzenes tested, only 1,2,4,5-tetrachlorobenzene and hexachlorobenzene promoted the occurrence of DENA-initiated GGT foci. Thus in rat liver, the tested by-products of drinking water disinfection did not demonstrate tumor-initiating activity, although a few appeared to possess tumor-promoting activity. Chloroform was also tested for tumor-promoting activity in 15-day-old Swiss mice initiated with ethylnitrosourea (ENU). At weaning they started to receive either 1800 ppm chloroform or 500 ppm sodium phenobarbital (the positive control for tumor promotion) in their drinking water. The mice continued to receive either chloroform or phenobarbital until 51 weeks of age and were sacrificed at 52 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Cabral J. R., Mollner T., Raitano F., Shubik P. Carcinogenesis of hexachlorobenzene in mice. Int J Cancer. 1979 Jan 15;23(1):47–51. doi: 10.1002/ijc.2910230110. [DOI] [PubMed] [Google Scholar]
  2. Cohen S. M., Arai M., Jacobs J. B., Friedell G. H. Promoting effect of saccharin and DL-tryptophan in urinary bladder carcinogenesis. Cancer Res. 1979 Apr;39(4):1207–1217. [PubMed] [Google Scholar]
  3. Cohen S. M. Urinary bladder carcinogenesis: initiation-promotion. Semin Oncol. 1979 Jun;6(2):157–160. [PubMed] [Google Scholar]
  4. Columbano A., Rajalakshmi S., Sarma D. S. Requirement of cell proliferation for the initiation of liver carcinogenesis as assayed by three different procedures. Cancer Res. 1981 Jun;41(6):2079–2083. [PubMed] [Google Scholar]
  5. Diaz Gomez M. I., Castro J. A. Covalent binding of chloroform metabolites to nuclear proteins - no evidence for binding to nucleic acids. Cancer Lett. 1980 May;9(3):213–218. doi: 10.1016/0304-3835(80)90089-0. [DOI] [PubMed] [Google Scholar]
  6. Farber E. Carcinogenesis--cellular evolution as a unifying thread: Presidential address. Cancer Res. 1973 Nov;33(11):2537–2550. [PubMed] [Google Scholar]
  7. Ford J. O., Pereira M. A. Short-term in vivo initiation/promotion bioassay for hepatocarcinogens. J Environ Pathol Toxicol. 1980 Nov;4(5-6):39–46. [PubMed] [Google Scholar]
  8. Ford J. O., Pereira M. A. Short-term in vivo initiation/promotion bioassay for hepatocarcinogens. J Environ Pathol Toxicol. 1980 Nov;4(5-6):39–46. [PubMed] [Google Scholar]
  9. Goerttler K., Loehrke H., Schweizer J., Hesse B. Systemic two-stage carcinogenesis in the epithelium of the forestomach of mice using 7,12-dimethylbenz(a)anthracene as initiator and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate as promoter. Cancer Res. 1979 Apr;39(4):1293–1297. [PubMed] [Google Scholar]
  10. Hatch G. G., Mamay P. D., Ayer M. L., Casto B. C., Nesnow S. Chemical enhancement of viral transformation in Syrian hamster embryo cells by gaseous and volatile chlorinated methanes and ethanes. Cancer Res. 1983 May;43(5):1945–1950. [PubMed] [Google Scholar]
  11. Herren S. L., Pereira M. A., Britt A. L., Khoury M. K. Initiation/promotion assay for chemical carcinogens in rat liver. Toxicol Lett. 1982 Jul;12(2-3):143–150. doi: 10.1016/0378-4274(82)90177-1. [DOI] [PubMed] [Google Scholar]
  12. Herren S. L., Pereira M. A. Tumor promotion in rat liver. Environ Health Perspect. 1983 Apr;50:123–129. doi: 10.1289/ehp.8350123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kaufmann W. K., Kaufman D. G., Rice J. M., Wenk M. L. Reversible inhibition of rat hepatocyte proliferation by hydrocortisone and its effect on cell cycle-dependent hepatocarcinogenesis by N-methyl-N-nitrosourea. Cancer Res. 1981 Nov;41(11 Pt 1):4653–4660. [PubMed] [Google Scholar]
  14. Kirkland D. J., Smith K. L., Van Abbé N. J. Failure of chloroform to induce chromosome damage or sister-chromatid exchanges in cultured human lymphocytes and failure to induce reversion in Escherichia coli. Food Cosmet Toxicol. 1981 Oct;19(5):651–656. doi: 10.1016/0015-6264(81)90517-4. [DOI] [PubMed] [Google Scholar]
  15. Kitagawa T., Pitot H. C., Miller E. C., Miller J. A. Promotion by dietary phenobarbital of hepatocarcinogenesis by 2-methyl-N,N-dimethyl-4-aminoazobenzene in the rat. Cancer Res. 1979 Jan;39(1):112–115. [PubMed] [Google Scholar]
  16. Kitagawa T., Sugano H. Enhancing effect of phenobarbital on the development of enzyme-altered islands and hepatocellular carcinomas initiated by 3'-methyl-4-(dimethylamino) azobenzene or diethylnitrosamine. Gan. 1978 Oct;69(5):679–687. [PubMed] [Google Scholar]
  17. Matsukura N., Kawachi T., Sano T., Sasajima K., Sugimura T. Promoting action of croton oil on gastrocarcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in rats. J Cancer Res Clin Oncol. 1979 Apr 12;93(3):323–327. doi: 10.1007/BF00964588. [DOI] [PubMed] [Google Scholar]
  18. Mochizuki Y., Furukawa K., Sawada N., Gotoh M. Dose-dependent enhancing effect of phenobarbital on hepatocarcinogenesis initiated by diethylnitrosamine in the rat. Gan. 1981 Feb;72(1):170–173. [PubMed] [Google Scholar]
  19. Nishizumi M. Effect of phenobarbital, dichlorodiphenyltrichloroethane, and polychlorinated biphenyls on diethylnitrosamine-induced hepatocarcinogenesis. Gan. 1979 Dec;70(6):835–837. [PubMed] [Google Scholar]
  20. Nishizumi M. Enhancement of diethylnitrosamine hepatocarcinogenesis in rats by exposure to polychlorinated biphenyls or phenobarbital. Cancer Lett. 1976 Sep;2(1):11–15. doi: 10.1016/s0304-3835(76)80004-3. [DOI] [PubMed] [Google Scholar]
  21. Peraino C., Fry R. J., Staffeldt E. Brief communication: Enhancement of spontaneous hepatic tumorigenesis in C3H mice by dietary phenobarbital. J Natl Cancer Inst. 1973 Oct;51(4):1349–1350. doi: 10.1093/jnci/51.4.1349. [DOI] [PubMed] [Google Scholar]
  22. Pereira M. A., Herren-Freund S. L., Britt A. L., Khoury M. M. Effects of strain, sex, route of administration and partial hepatectomy on the induction by chemical carcinogens of gamma-glutamyltranspeptidase foci in rat liver. Cancer Lett. 1983 Sep;20(2):207–214. doi: 10.1016/0304-3835(83)90050-2. [DOI] [PubMed] [Google Scholar]
  23. Pereira M. A., Herren S. L., Britt A. L., Khoury M. M. Sex difference in enhancement of GGTase-positive foci by hexachlorobenzene and lindane in rat liver. Cancer Lett. 1982 Jan;15(1):95–101. doi: 10.1016/0304-3835(82)90081-7. [DOI] [PubMed] [Google Scholar]
  24. Pereira M. A., Herren S. L., Britt A. L., Khoury M. M. Sex difference in enhancement of GGTase-positive foci by hexachlorobenzene and lindane in rat liver. Cancer Lett. 1982 Jan;15(1):95–101. doi: 10.1016/0304-3835(82)90081-7. [DOI] [PubMed] [Google Scholar]
  25. Pereira M. A., Knutsen G. L., Herren-Freund S. L. Effect of subsequent treatment of chloroform or phenobarbital on the incidence of liver and lung tumors initiated by ethylnitrosourea in 15 day old mice. Carcinogenesis. 1985 Feb;6(2):203–207. doi: 10.1093/carcin/6.2.203. [DOI] [PubMed] [Google Scholar]
  26. Pereira M. A., Lin L. H., Lippitt J. M., Herren S. L. Trihalomethanes as initiators and promoters of carcinogenesis. Environ Health Perspect. 1982 Dec;46:151–156. doi: 10.1289/ehp.8246151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pereira M. A., Savage R. E., Jr, Herren S. L., Guion C. W. Comparison of enhancement of GGTase-positive foci and induction of ornithine decarboxylase in rat liver by barbiturates. Carcinogenesis. 1982;3(2):147–150. doi: 10.1093/carcin/3.2.147. [DOI] [PubMed] [Google Scholar]
  28. Pereira M. A., Stoner G. D. Comparison of rat liver foci assay and strain A mouse lung tumor assay to detect carcinogens: a review. Fundam Appl Toxicol. 1985 Aug;5(4):688–699. doi: 10.1016/0272-0590(85)90193-9. [DOI] [PubMed] [Google Scholar]
  29. Pitot H. C., Goldsworthy T., Campbell H. A., Poland A. Quantitative evaluation of the promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxin of hepatocarcinogenesis from diethylnitrosamine. Cancer Res. 1980 Oct;40(10):3616–3620. [PubMed] [Google Scholar]
  30. Preston B. D., Van Miller J. P., Moore R. W., Allen J. R. Promoting effects of polychlorinated biphenyls (Aroclor 1254) and polychlorinated dibenzofuran-free Aroclor 1254 on diethylnitrosamine-induced tumorigenesis in the rat. J Natl Cancer Inst. 1981 Mar;66(3):509–515. [PubMed] [Google Scholar]
  31. Reitz R. H., Fox T. R., Quast J. F. Mechanistic considerations for carcinogenic risk estimation: chloroform. Environ Health Perspect. 1982 Dec;46:163–168. doi: 10.1289/ehp.8246163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Roe F. J., Palmer A. K., Worden A. N., Van Abbé N. J. Safety evaluation of toothpaste containing chloroform. I. Long-term studies in mice. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):799–819. [PubMed] [Google Scholar]
  33. Rutenburg A. M., Kim H., Fischbein J. W., Hanker J. S., Wasserkrug H. L., Seligman A. M. Histochemical and ultrastructural demonstration of gamma-glutamyl transpeptidase activity. J Histochem Cytochem. 1969 Aug;17(8):517–526. doi: 10.1177/17.8.517. [DOI] [PubMed] [Google Scholar]
  34. Scherer E. Neoplastic progression in experimental hepatocarcinogenesis. Biochim Biophys Acta. 1984;738(4):219–236. doi: 10.1016/0304-419x(83)90005-7. [DOI] [PubMed] [Google Scholar]
  35. Sturrock J. Lack of mutagenic effect of halothane or chloroform on cultured cells using the azaguanine test system. Br J Anaesth. 1977 Mar;49(3):207–210. doi: 10.1093/bja/49.3.207. [DOI] [PubMed] [Google Scholar]
  36. Tsuda H., Lee G., Farber E. Induction of resistant hepatocytes as a new principle for a possible short-term in vivo test for carcinogens. Cancer Res. 1980 Apr;40(4):1157–1164. [PubMed] [Google Scholar]
  37. Uchida E., Hirono I. Effect of phenobarbital on induction of liver and lung tumors by dimethylnitrosamine in newborn mice. Gan. 1979 Oct;70(5):639–644. [PubMed] [Google Scholar]
  38. Uehleke H., Werner T., Greim H., Krämer M. Metabolic activation of haloalkanes and tests in vitro for mutagenicity. Xenobiotica. 1977 Jul;7(7):393–400. doi: 10.3109/00498257709035798. [DOI] [PubMed] [Google Scholar]
  39. Van Abbé N. J., Green T. J., Jones E., Richold M., Roe F. J. Bacterial mutagenicity studies on chloroform in vitro. Food Chem Toxicol. 1982 Oct;20(5):557–561. doi: 10.1016/s0278-6915(82)80064-1. [DOI] [PubMed] [Google Scholar]
  40. Vesselinovitch S. D., Rao K. V., Mihailovich N., Rice J. M., Lombard L. S. Development of broad spectrum of tumors by ethylnitrosourea in mice and the modifying role of age, sex, and strain. Cancer Res. 1974 Oct;34(10):2530–2538. [PubMed] [Google Scholar]
  41. Ward J. M., Rice J. M., Creasia D., Lynch P., Riggs C. Dissimilar patterns of promotion by di(2-ethylhexyl)phthalate and phenobarbital of hepatocellular neoplasia initiated by diethylnitrosamine in B6C3F1 mice. Carcinogenesis. 1983 Aug;4(8):1021–1029. doi: 10.1093/carcin/4.8.1021. [DOI] [PubMed] [Google Scholar]
  42. Yager J. D., Jr, Yager R. Oral contraceptive steroids as promoters of hepatocarcinogenesis in female Sprague-Dawley rats. Cancer Res. 1980 Oct;40(10):3680–3685. [PubMed] [Google Scholar]

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