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Metabolites of diethylstilboestrol induce sister chromatid exchange in human cultured fibroblasts


Diethylstilboestrol (DES) is one of the few substances for which a clear association with carcinogenicity has been established in man1,2. Nevertheless, it is still widely used, mainly as a cheap oestrogen to increase the slaughter weight of beef3, but in spite of this it is not known if residues in the meat or metabolites excreted by the cattle are hazardous to man. It is also unknown whether there is a threshold dose below which DES is harmless. A threshold might be expected if a hormonal mechanism of carcinogenesis rather than metabolic activation to an electrophilically reactive species operates. This possibility was supported by the observations that DES, in contrast to most other carcinogens, failed to induce mutations in the Salmonella/microsome test4–6 or malignant transformations of eukaryotic cells in culture7. It is also disturbing that DES, one of the few known human carcinogens was negative in these two most widely used short-term tests introduced as fast early-warning systems for potential carcinogens. We now report that DES is positive in sister chromatid exchange (SCE) induction, a short-term test for which a high correlation with the carcinogenicity of the compounds tested has been observed8–10. Moreover, we show that metabolic activation was involved. Two different pathways leading to metabolites much more active in SCE induction than DES itself (‘proximate agents’) were established.

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  1. Herbst, A. L., Uhlfelder, H. & Poskanzer, D. C. New Engl. J. Med. 284, 878–881 (1971).

    Article  CAS  Google Scholar 

  2. Herbst, A. L., Cole, P., Colton, T., Robboy, S. J. & Scully, R. E. Am. J. Obstet, Gynecol. 128, 43–50 (1977).

    Article  CAS  Google Scholar 

  3. McLachlan, J. A. & Dixon, R. L. in Advances in Modern Toxicology Vol. 1 (eds Mehlman, M. A., Shapiro, R. E. & Blumenthal, H.) 423–428 (Wiley, New York, 1976).

    Google Scholar 

  4. McCann, J., Choi, E., Yamasaki, E. & Ames, B. N. Proc. natn. Acad. Sci. U.S.A. 72, 5135–5139 (1975).

    Article  ADS  CAS  Google Scholar 

  5. Anderson, D. & Styles, J. A. Br. J. Cancer 37, 924–930 (1978).

    Article  CAS  Google Scholar 

  6. Glatt, H. R., Metzler, M. & Oesch, F. Mutat. Res. 67, 113–121 (1979).

    Article  CAS  Google Scholar 

  7. Styles, J. A. Br. J. Cancer 37, 931–936 (1978).

    Article  CAS  Google Scholar 

  8. Perry, P. & Evans, H. J. Nature 258, 121–125 (1975).

    Article  ADS  CAS  Google Scholar 

  9. Popescu, N. C., Turnbull, D. & DiPaolo, J. A. J. natn. Cancer Inst. 59, 289–293 (1977).

    Article  CAS  Google Scholar 

  10. Abe, S. & Sasaki, M. J. natn. Cancer Inst. 58, 1635–1641 (1977).

    Article  CAS  Google Scholar 

  11. Metzler, M. J. Toxic. environ. Hlth. Suppl. 1, 28–35 (1977).

    Google Scholar 

  12. Ames, B. N., McCann, J. & Yamasaki, E. Mutat. Res. 31, 347–364 (1975).

    Article  CAS  Google Scholar 

  13. Paul, J. Cell and Tissue Culture 5th Edn (Churchill Livingston, Edinburgh, 1976).

    Google Scholar 

  14. Kato, H. Nature 251, 70–72 (1974).

    Article  ADS  CAS  Google Scholar 

  15. Metzler, M. & McLachlan, J. A. Biochem. biophys. Res. Commun. 85, 874–884 (1978).

    Article  CAS  Google Scholar 

  16. Rüdiger, H. W. et al. Nature 262, 290–292 (1976).

    Article  ADS  Google Scholar 

  17. Diamond, L. & Gelboin, H. V. Science 166, 1023–1025 (1969).

    Article  ADS  CAS  Google Scholar 

  18. Martin, C. N., McDermid, A. C. & Garner, R. C. Cancer Res. 38, 2621–2627 (1978).

    CAS  PubMed  Google Scholar 

  19. Clive, D., Johnson, K. O., Spector, J. F. S., Batson, A. G. & Brown, M. M. M. Mutat. Res. 59, 61–108 (1979).

    Article  CAS  Google Scholar 

  20. McLachlan, J. A., Metzler, M. & Lamb, J. C. Life Sci. 23, 2521–2524 (1978).

    Article  CAS  Google Scholar 

  21. Kirkman, H. & Bacon, R. L. Cancer Res. 10, 122–123 (1950).

    CAS  PubMed  Google Scholar 

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Rüdiger, H., Haenisch, F., Metzler, M. et al. Metabolites of diethylstilboestrol induce sister chromatid exchange in human cultured fibroblasts. Nature 281, 392–394 (1979).

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