SPONTANEOUS CHROMOSOMAL-ABERRATIONS IN FANCONI-ANEMIA, ATAXIA-TELANGIECTASIA FIBROBLAST AND BLOOMS SYNDROME LYMPHOBLASTOID CELL-LINES AS DETECTED BY CONVENTIONAL CYTOGENETIC ANALYSIS AND FLUORESCENCE IN-SITU HYBRIDIZATION (FISH) TECHNIQUE

Several primary and transformed human cell lines derived from cancer p rone patients are employed routinely for biochemical and DNA repair st udies. Since transformation leads to some chromosomal instability a cy togenetic analysis of spontaneous chromosome aberrations in fibroblast cell lines derived from patients with Fanconi anaemia (FA), ataxia te langiectasia (AT), and in lymphoblastoid cell lines derived from patie nts with Bloom's syndrome (BS), was undertaken. Unstable aberrations w ere analysed in Giemsa stained preparations and the chromosome paintin g technique was used for evaluating the frequencies of stable aberrati ons (translocations). In addition, the frequency of sister-chromatid e xchanges (SCEs) was determined in differentially stained metaphases. T he SV40-transformed fibroblasts from these cell lines have higher freq uencies of unstable aberrations than the primary fibroblasts. In the f our lymphoblastoid cell lines derived from BS patients higher frequenc ies of spontaneously occurring chromosomal aberrations in comparison t o normal TK6wt cells were also evident. The frequency of spontaneously occurring chromosome translocations was determined with fluorescence in situ hybridisation (FISH) and using DNA libraries specific for chro mosomes 1, 2, 3, 4, 7, 8, 11, 14, 19, 20 and X. The translocation leve ls were found to be elevated for primary FA fibroblasts and lymphoblas toid cells derived from BS patients in comparison with control cell li nes, hetero- and homozygote BS cell lines not differing in this respec t. The SV40-transformed cell lines showed very high frequencies of tra nslocations independent of their origin and almost every cell containe d at least one translocation. In addition, clonal translocations were found in transformed control TK6wt and AT cell lines for chromosomes 2 0 and 14, respectively. The spontaneous frequencies of SCEs were simil ar in transformed fibroblasts derived from normal individuals and AT p atients, whereas in SV40-transformed FA cells these were higher (4-fol d). Among cell lines derived from BS patients, heterozygote lines beha ved like control, whereas in homozygote cell lines very high frequenci es of SCEs (about 12-fold) were evident.