Summary
Peripheral blood lymphocytes from three patients with Down syndrome (DS; trisomy 21; aged 5–6 years) and three age-matched control children were studied for the induction of chromosomal aberrations and sister chromatid exchanges (SCEs).
Cells in G0 were exposed to bleomycin (20–100 μg/ml) for 3 h, and then cultured in medium containing 5-bromodeoxyuridine and phytohemagglutinin for 66 h. By the sister chromatid differential staining method, chromosome analyses were performed on metaphase cells that had divided one, two, or three or more times after treatment. The results indicate that DS cells exposed to bleomycin are hypersensitive to the production of dicentric and ring chromosomes compared to normal cells. Bleomycin also led to a dose-related increase in the frequency of SCEs, but no difference was found between the SCE frequencies in DS or normal lymphocytes exposed to bleomycin.
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References
Banerjee A, Benedict W (1979) Production of sister chromatid exchanges by various cancer chemotherapeutic agents. Cancer Res 39:797–799
Bienkowska ZM, Dawson KB, Peacock JH (1973) Action of actinomycins, bleomycin and X-rays on HeLa cells. Br J Radiol 46: 619–622
Bornstein RS, Hungerford DA, Haller G, Engstrom PF, Yarboro JW (1971) Cytogenetic effects of bleomycin therapy in man. Cancer Res 31:2004–2007
Dekaban AT, Thron R, Steusing JK (1966) Chromosomal aberrations in irradiated blood and blood cultures of normal subjects and of selected patients with chromosomal abnormalities. Radiat Res 27:50–63
Dresp J, Schmid E, Bauchinger M (1978) The cytogenetic effect of bleomycin on human peripheral lymphocytes in vitro and in vivo. Mutat Res 56:341–353
Gebhart E, Kappauf H (1978) Bleomycin and sister-chromatid exchange in human lymphocyte chromosome. Mutat Res 58: 121–124
Goto K, Maeda S, Kano Y, Sugiyama T (1978) Factors involved in differential Giemsa-staining of sister chromatids. Chromosoma (Berl) 66:351–359
Harnden DG (1976) Chromosome abnormalities and predisposition towards cancer. Proc R Soc Med 69:41–45
Higurashi M, Conen PE (1973) In vivo chromosomal radiosensitivity in “chromosomal breakage syndromes”. Cancer 32:380–383
Higurashi M, Tamura T, Nakataka T (1973) Cytogenetic observations in cultured lymphocytes from patients with Down's syndrome and measles. Pediat Res 7:582–587
Higurashi M, Tada A, Miyahara S, Hirayama M, Hoshina H, Tamura T (1976) Chromosome damage in Down's syndrome induced by chickenpox infection. Pediat Res 10:189–192
Holland WW, Doll R, Carter CO (1962) The mortality from leukemia and other cancer among patients with Down's syndrome (monglos) and among their parents. Br J Cancer 16:177–186
Kihlman BA, Sturelid S, Hartly-Asp B, Nilson K (1974) The enhancement by caffein of the frequencies of chromosomal aberrations induced in plant and animal cells by chemical and physical agents. Mutat Res 26:105–122
Kucerova M, Polikova Z (1978) In vitro comparison of normal and trisomic cell sensitivity to physical and chemical mutagens. In: Evans HJ, Lloyd DC (eds) Mutagen-induced chromosome damage in man. University Press, Edinburgh, pp 185–190
Littlefield LG, Colyer SP, Sayer AM, Dufrain RJ (1979) Sisterchromatid exchanges in human lymphocytes exposed during G0 to four classes of DNA-damaging chemicals. Mutat Res 67: 259–269
Morimoto K, Wolff S (1980a) Cell cycle kinetics in human lymphocyte cultures. Nature 288:604–606
Morimoto K, Wolff S (1980b) Increase of sister chromatid exchanges and perturbations of cell division kinetics in human lymphocytes by benzene metabolites. Cancer Res 40:1189–1193
Morimoto K, Kaneko T, Iijima K, Koizumi A (1984) Proliferative kinetics and chromosome damage in trisomy 21 lymphocyte cultures exposed to gamma-rays and bleomycin. Cancer Res (in press)
Morten JE, Harnden DG, Tayler AMR (1981) Chromosome damage in G0 X-irradiated lymphocytes from patients with hereditary retinoblastoma. Cancer Res 41:3635–3638
Müller WE, Yamazaki Z, Breter HJ, Zahn RC (1972) Action of bleomycin on DNA and RNA. Eur J Biochem 31:518–525
O'Brien RL, Poon P, Kline E, Parker JW (1971) Suseptibility of chromosomes of patients with Down's syndrome to 7,12-dimethylbenz(a)antracene-induced aberrations in vitro. Int J Cancer 8:202–210
Ockey CH (1980) Differences between ‘spontaneous’ and induced sister-chromatid exchanges with fixation time and their chromosome localization. Cytogenet Cell Genet 26:223–235
Ohama K, Kadotani T (1970) Cytogenetic effects of bleomycin on cultured human leukocytes. Jpn J Hum Genet 14:293–297
Paika K, Krishan A (1973) Bleomycin induced chromosomal aberrations in cultured mammalian cells. Cancer Res 33:961–965
Paul PWB, Goudzward JH (1980) Bleomycin-induced structural chromosomal aberrations in spermatogonia and bone-marrow cells of mice. Mutat Res 69:319–324
Perry PE, Evans HJ (1975) Cytological detection of mutagen carcinogen exposure by sister chromatid exchange. Nature 258:121–125
Preston RJ (1981) X-ray-induced chromosome aberrations in Down lymphocytes: An explanation of their increased sensitivity. Environ Mutagen 3:85–89
Promchainant C (1975) Cytogenetic effect of bleomycin on human leukocytes in vitro. Mutat Res 28:107–112
Ross SL, Moses RE (1978) Two actions of bleomycin on superhelical DNA. Biochemistry 17:581–586
Sasaki MS, Tonomura A, Matsubara S (1970) Chromosome constitution and its bearing on the chromosomal radiosensitivity in man. Mutat Res 10:617–633
Schinzel A, Schmid W (1976) Lymphocytes chromosome studies in humans exposed to chemical mutagens: The validity of the method in 67 patients under cytostatic therapy. Mutat Res 40: 139–166
Snope AJ, Rary JM (1979) Cell-cycle duration and sister-chromatid exchange frequency in cultured human lymphocytes. Mutat Res 63:345–349
Sognier MA, Hittelman WN, Pollard M (1982) The relationship between DNA and chromosome damage after bleomycin treatment: Dose-response measurements. Mutat Res 93:149–159
Sugimoto Y, Higurashi M, Iijima K, Hirayama M, Tanaka F (1982) Effects of Mitomycin C on the frequency of sister chromatid exchanges in lymphocytes cultured from patients with Down syndrome. Proc Jpn Acad 58(B):60–64
Suzuki H, Nagai K, Yamaki H, Tanaka N, Umezawa H (1969) On the mechanism of action of bleomycin scission of DNA strands in vitro and in vivo. J Antibiot 22:446–448
Tamura H, Sugiyama Y, Sugahara T (1974) Effect of bleomycin on the chromosomes of human lymphocytes at various cell phase. Gann 65:103–107
Terasima T, Yasukawa M, Umezawa H (1970) Breaks and rejoining of DNA in cultured mammalian cells treated with bleomycin. Gann 61:513–516
Tice R, Schneider EL, Pary JM (1976) The utilization of bromodeoxyuridine incorporation into DNA for the analysis of cellular kinetics. Exp Cell Res 102:232–236
Tobey RA (1972) Arrest of Chinese hamster cells in G2 following treatment with the antitumor drug bleomycin. J Cell Physiol 79: 259–265
Umezawa H, Asakura H, Oda K, Hori S (1973) The effect of bleomycin action on SV40 DNA: Characteristics of bleomycin action which produces a single scission in a superhelical form of SV40 DNA. J Antibiot 16:521–527
Vig BK (1979) Hyperthermic enhancement of chromosome damage and lack of effect on sister-chromatid exchanges induced by bleomycin in Chinese hamster cells in vitro. Mutat Res 61: 309–317
Vijayalaxmi, Evans HJ (1982) Bleomycin-induced chromosomal aberrations in Down's syndrome lymphocytes. Mutat Res 105: 107–113
Wolff S (1977) Sister chromatid exchange. Ann Rev Genet 11:183–201
Yamagami H, Ishizawa M, Endo H (1974) Phenotypic and genetic characteristics of bleomycin-sensitive strain of Escherichia coli. Gann 65:61–67
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Lijima, K., Morimoto, K., Koizumi, A. et al. Bleomycin-induced chromosomal aberrations and sister chromatid exchanges in Down lymphocyte cultures. Hum Genet 66, 57–61 (1984). https://doi.org/10.1007/BF00275187
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DOI: https://doi.org/10.1007/BF00275187