Summary
Chromosomal breakage frequencies were determined in Fanconi anaemia (FA) blood cultures treated with various concentrations of the polyfunctional alkylating agents mitomycin C, diepoxybutane, and cis-platinum(II)-diammine-dichloride, for which FA cells have a characteristic hypersensitivity. At concentrations that hardly affected control cultures, three out of four patients tested exhibited a concentration-dependent increase of cells with aberrant chromosomes, with a concomitant increase in the number of chromosomal aberrations per aberrant cell. The fourth patient, a 22-year-old male, was exceptional because with all three clastogens only 40% of his cultured cells exhibited a typical concentration-dependent response, while 60% of his cells responded like those from normal healthy controls. The possible nature and significance of this unusual response is discussed.
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References
Auerbach AD, Wolman SR (1976) Susceptibility of Fanconi's anaemia fibroblasts to chromosome damage by carcinogens. Nature 261:494–496
Auerbach AD, Adler B, Chaganti RSK (1981) Prenatal and postnatal diagnosis and carrier detection of Fanconi's anaemia by a cytogenetic method. Pediatrics 67:128–135
Bloom GE, Wagner S, Gerald PS, Diamond LK (1966) Chromosome abnormalities in constitutional aplastic anaemia. N Engl J Med 274:8–14
Cervenka J, Arthur D, Yasis C (1981) Mitomycin C test for diagnostic differentiation of idiopathic aplastic anemia and Fanconi's anemia. Pediatrics 67:119–127
Fanconi G (1927) Familiäre, infantile perniziosaartige Anämie. Jb Kinderheilkd 117:257–280
Fanconi G (1967) Familial constitutional panmyelocytopathy, Fanconi's anemia (F.A.). Semin Hematol 4:233–240
German J (1972) Genes which increase chromosome instability in somatic cells and predispose to cancer. Prog Med Gen 8:61–101
Glanz A, Fraser FC (1982) Spectrum of anomalies in Fanconi's anemia. J Med Genet 19:412–416
ISCN (1978) An international system for human cytogenetic nomenclature. Cytogenet Cell Genet 21:309–404
Joenje H, Frants RR, Arwert F, de Bruin GJM, Kontense PJ, Van de Kamp JJP, de Koning, J, Eriksson AW (1979) Erythrocyte superoxide dismutase deficiency in Fanconi's anaemia established by two indepedent methods of assay. Scand J Clin Lab Invest 39:759–764
Joenje H, Arwert F, Eriksson AW, de Koning H, Oostra AB (1981) Oxygen-dependence of chromosomal aberrations in Fanconi's anaemia. Nature 290:142–143
Miura K, Morimoto Y, Koizumi A (1983) Proliferative kinetics and mitomycin C-induced chromosomal damage in Fanconi's anemia lymphocytes. Hum Genet 63:19–23
Moorhead PS, Nowell PW, Mellman WJ, Batips DM, Hungerford DA (1960) Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res 20:613–617
Poll EHA, Arwert F, Joenje H, Eriksson AW (1982) Cytogenetic toxicity of antitumor platinum compounds in Fanconi's anaemia. Hum Genet 61:228–230
Sasaki MS, Tonomura A (1973) A high susceptibility of Fanconi's anemia to chromosome breakage by DNA cross-linking agents. Cancer Res 33:1829–1836
Schroeder TM, Anschütz F, Knopp A (1964) Spontane Chromosomen-Aberrationen bei familiärer Panmyelopathy. Hum Genet 1:194–196
Schroeder TM, Kurth R (1971) Spontaneous chromosomal breakage and high incidence of leukemia in inherited disease. Blood 87:96–112
Schroeder TM (1982) Genetically determined chromosome instability syndromes. Cytogenet Cell Genet 33:119–132
Swift MR, Hirschhorn K (1966) Fanconi's anaemia. Inherited susceptibility to chromosome breakage in various tissues. Ann Int Med 65:496–503
Swift M (1971) Fanconi's anaemia in the genetics of neoplasia. Nature 230:370–373
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Kwee, M.L., Poll, E.H.A., van de Kamp, J.J.P. et al. Unusual response to bifunctional alkylating agents in a case of Fanconi anaemia. Hum Genet 64, 384–387 (1983). https://doi.org/10.1007/BF00292372
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DOI: https://doi.org/10.1007/BF00292372