Cells from persons with Bloom's syndrome (BS) show many more sister chromatid exchanges (SCEs) than cells from normal individuals or those with any other genetic disease studied so far1. Several other abnormalities demonstrable in cell culture (reviewed in ref. 2) suggest that the molecular defect in BS is related to DNA metabolism; for example, many chromosomal aberrations in untreated cells3, abnormally slow DNA chain growth4,5, and increased sensitivity to treatment with ethyl methanesulphonate6,7. BS cells respond as normal cells do in excision repair8–10, ‘post-replication repair’11, and repair of single-strand breaks12. This apparent proficiency at repair prompted the suggestion13,14 that the various chromosome abnormalities result from an excessive accumulation spontaneously of lesions in the DNA on which a repair system(s) must act, thereby overloading the system(s). Such lesions might result, for example, from the action of a genetically defective enzyme involved in the semi-conservative replication of DNA, a defect leading to a quantitative imbalance in a chromosomal component, or a defect leading to the intrinsic production of a molecule with mutagenic properties. Experiments designed to test this last possibility have resulted in conflicting reports15–18. We report here results which do not support the hypothesis that BS cells release such a mutagenic molecule. SCE frequencies in non-BS cells were not affected when the cells were placed in contact-dependent metabolic coupling with BS cells. Also, when we repeated experiments15 in which medium ‘conditioned’ by BS fibroblasts was reported to increase the amount of SCE in normal blood lymphocytes, we were unable to duplicate those results.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Chaganti, R. S. K., Schonberg, S. & German, J. Proc. natn. Acad. Sci. U.S.A. 71, 4508–4512 (1974).
German, J. & Schonberg, S. in Genetic and Environmental Factors in Experimental and Human Cancer (eds Gelboin, H. V. et al.) (University of Tokyo Press, in the press).
German, J., Archibald, R. & Bloom, D. Science 148, 506–507 (1965).
Hand, R. & German, J. Proc. natn. Acad. Sci. U.S.A. 72, 758–762 (1975).
Giannelli, F., Benson, P. R., Pawsey, S. A. & Polani, P. E. Nature 265, 466–469 (1977).
Krepinsky, A. B., Heddle, J. A. & German, J. Hum. Genet. 50, 151–156 (1979).
Arlett, C. F. & Harcourt, S. A. in DNA Repair Mechanisms (eds Hanawalt, P. C., Friedberg, E. C. & Fox, C. F.) 633–636 (Academic, New York, 1978).
Ahmed, F. E. & Setlow, R. B. Biochim. biophys. Acta 521, 805–817 (1978).
Evans, H. J., Adams, A. C., Clarkson, J.M. & German, J. Cytogenet. Cell Genet. 20, 124–140 (1978).
Cleaver, J. J. invest. Derm. 54, 181–195 (1970).
Lehmann, A. R., Kirk-Bell, S. & Jaspers, N. G. J. in DNA Repair Processes (eds Nichols, W. W. & Murphy, D. G.) 203–215 (Symposia Specialists, Miami, 1977).
Vincent, R. A. Jr., Hays, M. D. & Johnson, R. C. in DNA Repair Mechanisms (eds Hanawalt, P. C., Friedberg, E. C. & Fox, C. F.) 663–666 (Academic, New York, 1978).
German, J. in DNA Repair Mechanisms (eds Hanawalt, P. C., Friedberg, E. C. & Fox, C. F.) 625–631 (Academic, New York, 1978).
Tice, R. R., Rary, J. M. & Bender, M. A. in DNA Repair Mechanisms (eds Hanawalt, P. C., Friedberg, E. C. & Fox, C. F.) 659–662 (Academic, New York, 1978).
Tice, R., Windler, G. & Rary, J. M. Nature 273, 538–540 (1978).
van Buul, P. P. W., Natarajan, A. T. & Verdegaal-Immerzeel, E. A. M. Hum. Genet. 44, 187–189 (1978).
Bartram, C. R., Rüdiger, H. W. & Passarge, E. Hum. Genet. 46, 331–334 (1979).
Rüdiger, H. W., Bartram, C. R., Harder, W. & Passarge, E. Am. J. hum. Genet. (in the press).
Littlefield, J. W. Science 145, 709–710 (1964).
Subak-Sharpe, H., Burk, R. & Pitts, J. E. J. Cell Sci. 4, 353–367 (1969).
Pitts, J. D. in International Cell Biology 1976–1977 (eds Brinkley, B. R. & Porter, K. R.) 43–49 (Rockefeller University Press, New York, 1977).
Bryant, E. M., Hoehn, H. & Martin, G. M. Nature 279, 795–796 (1979).
Bartram, C. R., Koske-Westphal, T. & Passarge, E. Ann. hum. Genet., Lond. 40, 79–86 (1976).
Flagg-Newton, J., Simpson, I. & Lowenstein, W. R. Science 205, 404–407 (1979).
Fishbein, L. in Advances in Modern Toxicology (eds Flamm, W. G. & Mehlman, M. A.) 175–348 (Wiley, New York, 1978).
German, J., Bloom, D. & Passarge, E. Clin. Genet. 12, 162–168 (1977); 15, 361–367 (1979).
German, J., Schonberg, S., Louie, E. & Chaganti, R. S. K. Am. J. hum. Genet. 29, 248–255 (1977).