Summary
Down syndrome (DS) is one of the most common types of congenital anomalies. In addition to a wide spectrum of developmental abnormalities, DS patients are also highly sensitive to the induction of chromosomal aberrations when their G0 lymphocytes are exposed to ionizing radiation. We conducted the present study to evaluate the effect of X-rays on proliferating lymphocytes from DS and normal individuals. We found that DS lymphocytes were significantly more sensitive to X-ray induction of chromosome aberrations than normal cells, when they were irradiated at the G0, G1 and S phases of the cell cycle. The S phase was the most radiosensitive phase and would lead to extensive cell killing, whereas the G1 phase seemed to be more prone to the induction of chromosome rearrangements that would potentially lead to serious long-term consequences.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Antoine JL, Dutrillaux B (1984) Chromosomal consequences of irradiation of human lymphocytes during S-phase, with special reference to chromatid exchanges. Mutat Res 129:173–179
Athanasiou K, Bartsocas CS (1982) The implications of S-phase exchanges for the mechanisms of radiosensitivity in Trisomy 21. Am J Med Genet 12:141–146
Athanasiou K, Sideris EG, Bartsocas C (1980) Decreased repair of X-ray induced DNA single strand breaks in lymphocytes in Down syndrome. Pediatr Res 14:336–338
Au WW, Luippold H (1982) Sister chromatid differentiation analysis of cell kinetics in mouse bone marrow cells. Environ Mutagen 4:376
Boyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest [Suppl 97] 21:77–89
Carrano AV (1975) Induction of chromosomal aberrations in human lymphocytes by X-rays and fissien neutrons: dependence on cell cycle stages. Radiat Res 63:403–421
Chudina AP (1968) A study of radiosensitivity of chromosomes in normal persons and in cases of Down's disease. Genetika 6:99–110
Chudina AP, Malyutina TS, Pogosyants HE (1968) Comparative radiosensitivity of chromosome in the cultured peripheral blood lymphocytes of normal donors and patients with Down's syndrome. Genetika 4:51–63
Conen PE, Erkman B (1966) Combined mongolism and leukemia: report of 8 cases with chromosome studies. Am J Dis Child 112:429
Countryman PI, Heddle JA, Crawford E (1977) The repair of X-ray induced chromosome damage in trisomy 21 and normal lymphocytes. Cancer Res 37:52–58
Crossen PE, Morgan WF (1977) Analysis of human lymphocytes cell-cycle time in culture measured by sister-chromatid differential staining. Exp Cell Res 104:453–457
Crossen PE, Morgan WF (1980) Lymphocyte proliferation in Down's syndrome measured by sister chromatid differential staining. Hum Genet 53:311–313
Edwards AA, Lloyd DC, Purrott RJ (1979) Radiation induced chromosome aberrations and the Poisson distribution. Radiat Environ Biophys 16:89–100
Goto K, Masda S, Keno Y, Sugiyama T (1977) Factors involved in differential Giemsa staining of sister chromatids. Chromosoma 66:351–359
Hieber L, Lucke-Huhle C (1983) PCC Technique reveals severechromatin lesions and repair in G2 arrested cells after alpha irradiation. Exp Cell Res 144:57–62
Krivet W, Good RA (1957) Simultaneous occurrence of mongolism and leukemia: report of a nationwide survey. Am J Dis Child 94:289
Leonard TC, Merz T (1983) The influence of cell-cycle kinetics in the radiosensitivity of Down's syndrome lymphocytes. Mutat Res 109:111–121
Miller RW (1970) Neoplasia and Down's syndrome. Ann NY Acad Sci 171:637
Morimoto K, Kaneko T, Iijima L Koizumi A (1984) Proliferation kinetics and chromosome damage in trisomy 21 lymphocyte cultures exposed to X-ray and bleomycin. Cancer Res 44:1499–1504
Otsuka F, Tarone RE, Seguin LR, Robbins JH (1985) Hypersensitivity of ionizing radiation in cultured cells from Down syndrome patients. J Neurol Sci 69:103–112
Preston RJ (1981) X-ray induced chromosome aberrations in Down lymphocytes: an explanation of their increased radiosensitivity. Environ Mutagen 3:85–89
Sasaki MS, Tonomura A, Matsubara S (1970) Chromosome constitution and its bearing on the chromosomal radiosensitivity in man. Mutat Res 10:617–633
Savage JRK (1975) Classification and relationships of induced-chromosomal structural changes. J Med Genet 12:103–122
Scott D, Zampetti-Bosseler F (1980) The relationship between cell killing, chromosome aberrations, spindle defects and mitotic delay in mouse lymphoma cells of differential sensitivity to X-rays. Int J Radiat Biol 37:33–47
Tice R, Schneider EL, Rary JM (1976) The utilization of bromodeoxyuridine incorporation into DNA for the analysis of cellular kinetics. Exp Cell Res 102:232–236
Todaro GJ, Martin GM (1967) Increased susceptibility of Down's syndrome fibroblasts to transformation by SV40. Proc Soc Exp Biol Med 124:1232–1236
Whorton EB Jr (1985) Some experimental design and analysis considerations for cytogenetic studies. Environ Mutagen [Suppl 4] 7:9–15
Whorton EB Jr, Kilian DJ (1981) The influence of multiple scorers on cytogenetics study results. Mutat Res 85:161–164
Yotti LP, Glover TW, Trosko JE, Segal DJ (1980) Comparative study of X-ray and UV induced cytotoxicity, DNA repair and mutagenesis in Down's syndrome and normal fibroblasts. Pediatr Res 14:88–92
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Shafik, H.M., Au, W.W. & Legator, M.S. Chromosomal radiosensitivity of Down syndrome lymphocytes at different stages of the cell cycle. Hum Genet 78, 71–75 (1988). https://doi.org/10.1007/BF00291238
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00291238