Summawre~airs chromosomal breaks (4). It was also re~orted that leukoUtilizing six age-matched human fibroblast cell strains (three normal and three Down's syndrome) cytotoxicity, DNA repair, and X-ray mutagenesis were measured. There was no significant difference in the colony-forming ability after ultraviolet (UV) or X-irradiation between normal and Down's fibroblasts. Similarly, UV-induced unscheduled DNA synthesis was not significantly different between normal and Down's cells. Finally, a comparison between the spontaneous and X-ray induced mutation frequency at the hypoxanthine-guanine phosphoribosyl transferase locus demonstrated no difference between the two cell types (normal and Down's). cy;es from Down's syndrome patients exhibitid lower levels of UV-induced DNA repair synthesis (unscheduled DNA synthesis) than did leukocytes from normal controls (10).In an attempt to further investigate the problem, the authors report here a series of experiments to measure: (1) colony-forming ability, i.e., survival, of Down's and normal fibroblasts exposed to either UV or X-irradiation, (2) unscheduled DNA synthesis (excision repair) of Down's and normal fibroblasts after exposure to UV, and (3) spontaneous and X-ray induced mutation frequencies at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus in Down's and normal fibroblasts.
Speculation
MATERIALS AND METHODS
Down's syndrome has long been recognized as a cancer-pronePrimary fibroblast cultures of age-and sex-matched normal and human syndrome. Chromosomal radiosensitivity indicated the pos-Down's syndrome individuals were provided by Dr. D. Segal sibility of faulty DNA repair leading to the accumulation of (Department of Pediatrics, University of Alberta, Edmonton, Alsomatic mutations. Because no biologic differences were detected berta). These cell strains have previously been examined in terms in fibroblasts, the predisposition to cancer (especially leukemia) in of their in vitro cell cycle, origin, and growth (18). The LeschDown's syndrome might be due to abnormal DNA repair in the Nyhan cells (GM 1362) were obtained from the Human Genetic white blood cells of these individuals.Mutant Cell Repository (Camden, NJ). The cells were grown in modified Eagle's medium (Earle's balanced salt solution with a 50% increase of essential amino acids and vitamins) supplemented It has been recognized now for many years that children with with "nonessential" amino acids (1Wo increase), 1 mM sodium Down's syndrome are at an increased risk for neoplasia, especially pyruvate, and 10% heat inactivated fetal calf serum. Under inculeukemia (8,9,14,15,20,22). In addition, chromosomes from bation conditions of 5% Con in humidxed air at 37OC the cells individuals who are trisomic for chromosome 21 exhibit an in-had a generation time of approximately 24 hr. creased aberration frequency (exchange type) after exposure toThe cell survival experiments were conducted similarly for UV gamma rays (17). Chromosomes from Down's syndrome individ-and X-irradiation. To determine th...