Common fragile sites: their prevalence in subjects with constitutional and acquired chromosomal instability.
Chromosomal fragile sites that are inducible by methotrexate and aphidicolin are frequent in the human population. To assess the frequency and distribution of these common fragile sites, we performed a cytogenetic survey on lymphocytes from subjects known to be particularly prone to breakage because of constitutional chromosomal instability, the possession of a rare fragile site, or Fanconi anemia. Furthermore, a group of cancer patients was included in this study in view of possible acquired chromosomal instability. Lymphocyte chromosomes from several healthy donors were analyzed under identical conditions. We found that methotrexate- and aphidicolin-induced fragile sites are widespread in the general population, showing a similar breakpoint distribution. Ten fragile sites (3p14, 16q23, 2q32, 6q25, 4p16, 4q31, 14q24, 1p31, 20p12, 7q21) were observed in at least 40% of the individuals among the different groups. Our data point out a significantly increased breakage induced by aphidicolin in lymphocytes from cancer patients and, to a lesser extent, from rare fragile sites carriers. These results suggest that common fragile sites are enhanced in some constitutional and acquired conditions.
D000230:Adenocarcinoma / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D016590:Aphidicolin; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000453:epidemiology* / Q000235:genetics; D025063:Chromosome Disorders; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology; D005199:Fanconi Anemia / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics
D004224:Diterpenes; D016590:Aphidicolin; D008727:Methotrexate