Summary
Chromosome studies were performed on peripheral lymphocytes from two patients with Werner syndrome and two healthy control individuals to detect spontaneous and/or mutagen-induced chromosomal instability of this disease. Diepoxybutane, isonicotinic acid hydrazide, 4-nitro-quinoline-1-oxide, and bleomycin were used as standard clastogens. While the spontaneous frequency of chromosomal breakage was much higher in lymphocytes from both patients than in the control cells, the basic rate of sister chromatid exchange (SCE) was found to be in the control range. The sensitivity to clastogens of the patients' cells, however, was not substantially increased as compared with the controls if the degree of multiplication of the spontaneous breakage rate or SCE frequency was taken as the basis for comparison. No indication of a greater inhibition of proliferation by the clastogens in the patients' cells than in normal cells was observed using BrdU-labelled lymphocytes. Thus, the lymphocytes from both patients of the present study lacked essential features of the classical chromosome instability syndromes.
Similar content being viewed by others
References
Auerbach AD, Wolman SR (1976) Susceptibility of Fanconi's anemia fibroblasts to chromosome damage by carcinogens. Nature 261:494–496
Auerbach AD, Wolman SR (1979) Carcinogen-induced chromosome breakage in chromosome instability syndromes. Cancer Genet Cytogenet 1:21–28
Bartram CR, Koske-Westphal T, Passarge E (1976) Chromatid exchanges in ataxia telangiectasia, Bloom's syndrome, Werner's syndrome, and xeroderma pigmentosum. Ann Hum Genet 40:79–86
Brown WT (1983) Werner's syndrome. In: German J (ed) Chromosome mutation and neoplasia. Liss, New York, pp 85–93
Darlington GJ, Dutkowski R, Brown WT (1981) Sister chromatid exchange frequency in progeria and Werner syndrome patients. Am J Hum Genet 33: 762–766
Fujiwara Y, Higashikawa T, Tatsumi M (1977) A retarded rate of DNA replication and normal level of DNA repair in Werner's syndrome fibroblasts in culture. J Cell Physiol 92: 365–374
Gebhart E, Kappauf H (1978) Bleomycin and sister chromatid exchange in human lymphocyte chromosomes. Mutat Res 58: 121–124
Gebhart E, Wagner H, Behnsen H (1984) The action of anticlastogens in human lymphocyte cultures and its modification by rat liver S9 mix. I. Studies with AET and sodium fluoride. Mutat Res 129: 195–206
Gebhart E, Kysela D, Matthee H, Nikol M (1985) Cytogenetic analyses utilizing various clastogens in two sibs with Fanconi anemia, their relatives, and control individuals. Hum Genet 69: 309–315
Heddle JA, Krepinsky AB, Marshall RR (1983) Cellular sensitivity to mutagens and carcinogens in the chromosome-breakage and other cancer-prone syndromes. In: German J (ed) Chromosome mutation and neoplasia. Liss, New York, pp 203–234
Hoehn H, Bryant EM, Au K, Norwood TH, Boman H, Martin GM (1975) Variegated translocation mosaicism in human skin fibroblast cultures. Cytogenet Cell Genet 15: 282–298
Nordenson I (1977) Chromosome breaks in Werner's syndrome and their prevention in vitro by radical-scavenging enzymes. Hereditas 87: 151–154
Ray JH, German J (1983) The cytogenetics of the “chromosome breakage syndromes”. In: German J (ed) Chromosome mutation and neoplasia. Liss, New York, pp 135–167
Salk D (1982) Werner's syndrome: A review of recent research with analysis of connective tissue metabolism, growth control of cultured cells, and chromosomal aberrations. Hum Genet 62: 1–15
Salk D, Au K, Hoehn H, Martin GM (1981) Cytogenetics of Werner syndrome cultured skin fibroblasts: Variegated translocation mosaicism. Cytogenet Cell Genet 30: 92–107
Scappatticci S, Cerimele D, Fraccaro M (1982) Clonal structural chromosomal rearrangements in primary fibroblast cultures and in lymphocytes of patients with Werner's syndrome. Hum Genet 62: 16–24
Schonberg SA, Henderson E, Niermeijer MF, Bootsma D, German J (1981) Werner's syndrome: Preferential proliferation of clones with translocations. Am J Hum Genet 33: 120A
Schonberg S, Henderson E, Niermeijer MF, Bootsma D, German J (1983) Werner's syndrome: Preferential proliferation in vitro of clones with chromosome translocations. Cited from: German J (ed) Chromosome mutation and neoplasia. Liss, New York
Schroeder TM, Stahl-Maugé C (1979) Mutagenic effects of isonicotinic acid hydrazide in Fanconi's anemia. Hum Genet 52: 309–321
Tollefsbol TO, Cohen HJ (1984) Werner's syndrome: An underdiagnosed disorder resembling premature aging. Age 7: 75–88
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gebhart, E., Schinzel, M. & Ruprecht, K.W. Cytogenetic studies using various clastogens in two patients with Werner syndrome and control individuals. Hum Genet 70, 324–327 (1985). https://doi.org/10.1007/BF00295370
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00295370