Skip to main content
SpringerLink
Log in

Cytotoxic, mutagenic, and cell-cell communication inhibitory properties of DDT, lindane, and chlordane on Chinese hamster cellsin vitro

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

The cytotoxicity, mutagenicity, andin vitro inhibition of metabolic cooperation of DDT, lindane, and chlordane were studied with Chinese hamster V79 cells. The results showed differential cytotoxicity of these three pesticides (lindane < DDT < chlordane). There was no detectable mutagenic activity of any of these pesticides, using two genetic markers (6-thioguanine and diphtheria toxin resistance). DDT and lindane, however, were shown to have properties similar to 12-O-tetradecanoylphobol-13-acetate (a powerful mouse skin tumor promoter). Above what appeared to be a threshold level, there was a clear dose response of DDT and lindane in thein vitro cell-cell communication assay. Chlordane, which was the most cytotoxic pesticide tested, did not inhibit metabolic cooperation as significantly as did DDT or lindane. The role of these pesticides in carcinogenesis was speculated as being their tumor promoting properties, either at non-cytotoxic levels by mimicing TPA-like membrane alterations or at cytotoxic levels by mimicing partial hepatectomy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Agthe, C., H. Garcia, R. Shubik, L. Tomatis, and E. Wenyon: Study of the potential carcinogenicity of DDT in Syrian golden hamster (34740). Proc. Soc. Exp. Med. (N.Y.)134, 113 (1970).

    Google Scholar 

  • Ahmed, F. E., R. W. Hart, and N. J. Lewis: Pesticide-induced DNA damage and its repair in cultured human cells. Mutation Res.12, 161 (1977).

    Google Scholar 

  • Argyris, T. S., and T. J. Slaga: Promotion of carcinogenesis by repeated abrasion in initiated skin of mice. Cancer Res.41, 5193 (1981).

    PubMed  Google Scholar 

  • Argyris, T. S.: Tumor promotion by regenerative epidermal hyperplasia in mouse skin. J. Cutan. Pathol.9, 1 (1982).

    PubMed  Google Scholar 

  • Boutwell, R. K.: Biochemical mechanism of tumor promotion. In T. J. Slaga, A. Sivak, and R. K. Boutwell (eds.): Carcinogenesis. Vol. 2, p. 49. New York: Raven Press (1978).

    Google Scholar 

  • Cabral, J. R. R., and P. Shubik: Lack of carcinogenicity of DDT in hamster. Fed. Proc.36, 1086 (1977).

    Google Scholar 

  • Chang, C. C., J. E. Trosko, and T. Akera: Characterization of ultra-violet light-induced ouabain-resistant mutations in Chinese hamster cells. Mutation Res.51, 85 (1978).

    PubMed  Google Scholar 

  • Chang, C. C., J. E. Trosko, and T. W. Glover: Characterization of radiation-induced diphtheria toxin-resistant mutations in Chinese hamster V79 cells. 10th Annual Meeting of Environmental Mutagen Society Abstract, p. 96 (1979).

  • Craddock, V. M.: Liver carcinomas induced in rats by single administration of dimethylnitrosamine after partial hepatectomy. J. Natl. Cancer Inst.47, 889 (1971).

    Google Scholar 

  • Diamond, L., T. G. O'Brien, and G. Rovera: Tumor Promoters: Effects on proliferation and differentiation of cells in culture. Life Science23, 1979 (1978).

    Google Scholar 

  • Eagle, H.: Amino acid metabolism in mammalian cell culture. Science130, 432 (1959).

    PubMed  Google Scholar 

  • Enomoto, T., Y. Sasaki, Y. Shiba, Y. Kanno, and H. Yamasaki: Inhibition of the formation of electrical cell coupling of FL cells by tumor promoters. Gann72, 631 (1981a).

    PubMed  Google Scholar 

  • —, —, —: Tumor promoters cause a rapid and reversible inhibition of the formation and maintenance of electrical cell coupling in culture. Proc. Natl. Acad. Sci.78, 5628 (1981b).

    PubMed  Google Scholar 

  • Epstein, S. S.: Carcinogenicity of heptachlor and chlordane. Sci. Total Environ.6, 103 (1976).

    PubMed  Google Scholar 

  • Fitzgerald, D. J., and A. N. Murray: Inhibition of intercellular communication by tumor-promoting phorbol esters. Cancer Res.40, 2935 (1979).

    Google Scholar 

  • Fitzhugh, O. G., and A. A. Nelson: The chronic oral toxicity of DDT (2.2-Bis-p-chlorophyenyl-1,1,1-trichloroethane). J. Pharmacol. Exp. Ther.89, 18 (1947).

    Google Scholar 

  • Ford, D. K., and G. Yerganian: Observation on the chromosomes of Chinese hamster cell in tissue culture. J. Natl. Cancer Inst.21, 393 (1958).

    PubMed  Google Scholar 

  • Frei, J. V.: Some mechanisms operative in carcinogenesis: A review. Chem.-Biol. Inter.13, 1 (1976).

    Google Scholar 

  • Glover, T. W., C. C. Chang, J. E. Trosko, and S-L Li: Ultraviolet light induction of diphtheria toxin-resistant mutants in normal and xeroderma pigmentosum human fibroblasts. Proc. Natl. Acad. Sci. U.S.A.76, 3982 (1979).

    PubMed  Google Scholar 

  • Goto, M., M. Hattori, and T. Miyagawa: Contributions to ecological chemistry II. Hepatoma development in mice after administration of HCH isomers in high dosages. Chemosphere,1, 279 (1972).

    Google Scholar 

  • Griffin III, D. E., and W. E. Hill:In vitro breakage of plasmid DNA by mutagenes and pesticides. Mutation Res.52, 161 (1978).

    PubMed  Google Scholar 

  • Heddle, J. A., and W. R. Bruce: Comparison of tests for mutagenicity or carcinogenicity using assays for sperm abnormalities formation of micronuclei, and mutations inSalmonella. In H. E. Hiatt, J. D. Watson, and J. A. Winsten (eds.): Origins of human cancer. Cold Spring Harbor, Cold Spring Harbor Lab. (1977).

    Google Scholar 

  • Hanada, M., C. Yutani, and T. Miyaji: Induction of hepatoma in mice by benzene hexachloride. Gann65, 511 (1973).

    Google Scholar 

  • Horton, A. W., D. N. Eshleman, A. R. Schuff, and W. H. Perman: Correlation of cocarcinogenic activity amongn-alkanes with their physical effects on phospholipid micelles. J. Natl. Cancer Inst.56, 387 (1976).

    PubMed  Google Scholar 

  • IARC Monographs on the Evaluation of Carcinogenic Risk to Man, DDT and associated substances. Lyon. International Agency for Research on Cancer, Vol. 5 (1974).

  • Innes, J. R. M., B. M. Ulland, M. Valerio, L. Petrucelli, L. Fishbein, E. R. Hart, A. J. Pallotta, R. R. Bates, H. L. Falk, J. J. Gart, M. Klein, I. Michell, and J. Peters: Bioassay of pesticides and industrial chemicals for tumorigenicity in mice, A preliminary note. J. Natl. Cancer Inst.42, 1101 (1969).

    PubMed  Google Scholar 

  • Jensen, R. K., S. D. Sleight, S. D. Aust, J. I. Goodman, and J. E. Trosko: Hepatic tumor promotion by 3,3′,4,4′, 5,5′-hexabromobiphenyl: The interrelationship between toxicity, induction of microsomal drug metabolizing enzymes and tumor promotion. Submitted.

  • Johnson, G. A., and S. M. Jalal: DDT-induced chromosomal damage in mice. J. Hered.64, 7 (1973).

    PubMed  Google Scholar 

  • Kelly-Garvert, F., and M. S. Legator: Cytogenetic and mutagenic effects of DDT and DDE in Chinese hamster cell line. Mutation Res.17, 223 (1973).

    PubMed  Google Scholar 

  • Kinsella, A. R.: Investigation of the effects of the phorbol ester TPA on carcinogen-induced forward mutagenesis to 6-thioguanine-resistance in V79 Chinese hamster cells. Carcinogenesis2, 43 (1981).

    PubMed  Google Scholar 

  • Lagenbach, R., H. J. Freed, and E. Huberman: Liver cell-mediated mutagenesis of Mammalian cells by liver carcinogens. Proc. Natl. Acad. Sci. USA75, 2864 (1978).

    PubMed  Google Scholar 

  • Maher, V. M., and J. J. McCormick: Effect of DNA repair on the cytotoxicity and mutagenicity of UV irradiation and of chemical carcinogens in normal and xeroderma pigmentosum cells. In J. M. Yuhas, R. W. Tennant, and J. D. Regan (eds.): Biology of radiation carcinogenesis. New York: Raven Press (1976).

    Google Scholar 

  • Mrak, E. M. (Chairman): Report of the secretary's commission on pesticides and their relationship to environmental health, U.S. Dept. of Health, Education and Welfare, Washington, DC (1969).

    Google Scholar 

  • Marshall, T. C., H. W. Dorough, and H. E. Swim: Screening of pesticides for mutagenic potential usingSalmonella tryphimurin mutants. J. Agric. Food Chem.24, 560 (1976).

    PubMed  Google Scholar 

  • Matsumura, F., and S. M. Ghiasuddin: Characteristics of DDT sensitive Ca-ATPase in the axonic membrane. In T. Narahashi (ed.): Neurotoxicology of insecticides and phermones. New York: Plenum Press (1979).

    Google Scholar 

  • Matsumura, F., and K. C. Patil: Adenosine triphosphatase sensitive to DDT in synapses of rat brain. Science166, 121 (1969).

    PubMed  Google Scholar 

  • McCann, J., E. Choi, E. Yamasaki, and B. N. Ames: Detection of carcinogens as mutagens in theSalmonella/microsome test: Assay of 300 chemicals. Proc. Natl. Acad. Sci. USA72, 5135 (1975).

    PubMed  Google Scholar 

  • Murray, A. W., and D. J. Fitzgerald: Tumor promoters inhibit metabolic cooperation in cocultures of epidermal and 3T3 cells. Biochem. Biophys. Res. Commun.91, 395 (1979).

    PubMed  Google Scholar 

  • Nagao, M., T. Sugimura, and T. Matsushima: Environmental mutagens and carcinogens. Ann. Rev. Genet.12, 117 (1978).

    PubMed  Google Scholar 

  • Nagasaki, H., S. Tomii, T. Mega, M. Marugami, and N. Ito: Development of hepatomas in mice treated with benzene hexachloride. Gann62, 431 (1971).

    PubMed  Google Scholar 

  • Newbold, R. F., and J. Amos: Inhibition of metabolic cooperation between mammalian cells in culture by tumor promoters. Carcinogenesis2, 243 (1981).

    PubMed  Google Scholar 

  • Noda, K., M. Umeda, and I. Ono: Effects of various chemicals including bile acids and chemical carcinogens on the inhibition of metabolic cooperation. Gann72, 772 (1981).

    PubMed  Google Scholar 

  • Peraino, C., F. Michael, E. Staffeldt, and J. P. Christopher: Comparative enhancing effects of phenobarbital, amobarbital, diphenylhydantoin, and dichlorodiphenyl trichloroethane on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Cancer Res.35, 2884 (1975).

    PubMed  Google Scholar 

  • Pitot, H. C., and A. S. Sirica: The stages of initiation and promotion in hepatocarcinogens. Biochim. Biophys. Acta605, 191 (1980).

    PubMed  Google Scholar 

  • Planche, G., A. Croisy, L. Tomatis, and H. Bartsch: Metabolic and mutagenicity studies on DDT and 15 derivatives. Detection of 1,1-bis (p-chlorophenyl)-2,-2-dichloroethan and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethyl acetate (Kelthane acetate) as mutagens inSalmonella tryphirlum and of 1,1-bis(p-chlorophenyl)ethylene oxide, a likely metabolite, as an alkylating agent. Chem.-Biol. Inter.25, 157 (1979).

    Google Scholar 

  • Pound, A. W., and L. J. McGuire: Repeated partial hepatectomy as a promoting stimulus for carcinogenic response of liver to nitrosamines in rats. Br. J. Cancer37, 585 (1978).

    PubMed  Google Scholar 

  • Reuber, M. D.: Carcinomas and other lesions of the liver in mice ingesting organochlorine pesticides. Clin. Toxicol.13, 231 (1978).

    PubMed  Google Scholar 

  • —: Carcinogenicity of lindane. Environ. Res.19, 460 (1979).

    PubMed  Google Scholar 

  • Rinkus, S. J., and M. S. Legator: Chemical characterization of 465 known or suspected carcinogens and their correlation with mutagenic activity in theSalmonella tryphimurim system. Cancer Res.39, 3289 (1979).

    PubMed  Google Scholar 

  • Scribner, J. D., and N. K. Mottet: DDT acceleration of mammary gland tumors induced in the male Sprague-Dawley rat by 2-acetamidophenanthrene. Carcinogenesis2, 1235 (1981).

    PubMed  Google Scholar 

  • Shirasu, Y., M. Moriya, K. Kato, A. Furuhashi, and T. Kada: Mutagenicity screening of pesticides in the microbial system. Mutation Res.40, 19 (1976).

    PubMed  Google Scholar 

  • Shoyab, M., J. E. Delarco, and G. Todaro: Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors. Nature279, 387 (1979).

    Google Scholar 

  • Sivak, A., and B. L. Van Duuren: Cellular interactions of phorbol myristate acetate in tumor promotions. Chem.-Biol. Inter.3, 401 (1971).

    Google Scholar 

  • Slaga, T. J., S. M. Fisher, A. Viaje, D. L. Berry, W. M. Brachen, S. LeClerc, and D. R. Miller: Inhibition of tumor promotion by antiflammatory agents: An Approach to the biological mechanism of promotion. In T. J. Slaga, A. Sivak, and R. K. Boutwell (eds.): Carcinogenesis. New York: Raven Press. Vol. 2 (1978).

    Google Scholar 

  • Sternberg, S. S.: The carcinogenesis, mutagenesis, and teratogenesis of insecticides. Review of studies in animals and man. Pharmal. Ther.6, 147 (1979).

    Google Scholar 

  • Tarjan, R., and T. Kemeny: Multigeneration studies on DDT in mice. Fd. Cosmet. Toxicol.7, 215 (1969).

    Google Scholar 

  • Telang, S., C. Tong, and G. M. Williams: Epigenetic membrane effects of possible tumor promoting type or cultured liver cells by the nongenetic organochlorine pesticides, chlordane and heptachlor. Carcinogenesis3, 1175 (1982).

    PubMed  Google Scholar 

  • Trosko, J. E., and C. C. Chang: Environmental carcinogenesis: An integrative model. Q. Rev. Bio.53, 115 (1978a).

    Google Scholar 

  • —, —: The role of mutagenesis in carcinogenesis. In K. C. Smith (ed.): Photochemical and photobiological reviews. New York: Plenum Press, Vol. 3 (1978b).

    Google Scholar 

  • —, —: Chemical carcinogenesis as a consequence of alterations in the structure and function of DNA. In P. L. Grover (ed.): Chemical carcinogens and DNA. Boca Raton, FL: CRC Press, Vol. 2. (1979).

    Google Scholar 

  • —, —: Role of mutations and epigenetic changes in carcinogenesis: Correlations between chemical and radiation-induced carcinogenesis. In J. Lett and H. L. Adler (eds.): Advances in radiation biology. New York: Academic Press Vol. 9 (1981).

    Google Scholar 

  • Trosko, J. E., L. P. Yotti, S. T. Warren, G. Tsushimoto, and C. C. Chang: Inhibition of cell-cell communication by tumor promoters. In E. Hecker, N. E. Fusenig, W. Kunz, F. Marks, and H. W. Thielmann (eds.): Cocarcinogenesis, Biological effects of tumor promoters. New York: Raven Press Vol. 7. (1982a).

    Google Scholar 

  • Trosko, J. E., C. Jones, C. Aylsworth, and G. Tsushimoto: Elimination of metabolic cooperation is associated with the tumor promoters, oleic acid, and athralin. Carcinogenesis3, 1101 (1982b).

    PubMed  Google Scholar 

  • Umeda, M., K. Noda, and T. Ono: Inhibition of metabolic cooperation in Chinese hamster cells by various chemicals including tumor promoters. Gann71, 614 (1980).

    PubMed  Google Scholar 

  • Van Zeeland, A. A., and J. W. I. M. Simons: Linear dose-response relationships after prolonged expression times in V79 Chinese hamster cells. Mutation Res.35, 129 (1976).

    PubMed  Google Scholar 

  • Vogel, E.: Identification of carcinogens by mutagen testing in Drosophila: The relative reliability for the kinds of genetic damage measured. In H. H. Hiatt, J. D. Watson, and J. A. Winsten (eds.): Origin of cancer. Cold Spring Harbor: Cold Spring Harbor Lab. (1977).

    Google Scholar 

  • Weisburger, J. H., Z. Hadidian, T. N. Fredrickson, and E. K. Weisburger: Carcinogenesis by simultaneous action of several agents (Abstract). Toxicol. App. Pharmacol.7, 502 (1965).

    Google Scholar 

  • Welch, R. M., W. Levin, and A. H. Conney: Estrogenic action of DDT and its analog. Toxicol. App. Pharmacol.14, 358 (1969).

    Google Scholar 

  • Wenner, C. E., J. Hackney, H. K. Kimelberg, and E. Mayhow: Membrane effects of phobol esters. Cancer Res.34, 1731 (1974).

    PubMed  Google Scholar 

  • Williams, G. M., S. Telang, and C. Tong: Inhibition of intercellular communication between liver cells by the liver promoter 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane. Cancer Letters11, 339 (1981).

    PubMed  Google Scholar 

  • Witkin, E. M.: Relationships among repair, mutagenesis and survival: Overview. In P. C. Hanawalt, and R. B. Setlow (eds.): Molecular mechanisms for repair of DNA. New York: Plenum Press (1975).

    Google Scholar 

  • Yotti, L. P., C. C. Chang, and J. E. Trosko: Elimination of metabolic cooperation in Chinese hamster cells by a tumor promoter. Science206, 1089 (1979).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pesticide Research Center, Michigan State University, 48824, East Lansing, Michigan

    G. Tsushimoto & F. Matsumura

  2. Department of Pediatrics and Human Development, Michigan State University, 48824, East Lansing, Michigan

    C. C. Chang & J. E. Trosko

Authors
  1. G. Tsushimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. C. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. E. Trosko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Matsumura
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsushimoto, G., Chang, C.C., Trosko, J.E. et al. Cytotoxic, mutagenic, and cell-cell communication inhibitory properties of DDT, lindane, and chlordane on Chinese hamster cellsin vitro . Arch. Environ. Contam. Toxicol. 12, 721–729 (1983). https://doi.org/10.1007/BF01060757

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01060757

Keywords

Search

Navigation