On the localization of mitomycin C-induced aberrations in normal human and Fanconi's anaemia cells.
This paper summarizes the results of a series of experiments with primary cultures of normal human fibroblasts and lymphocytes designed to investigate chromatid aberration 'break-point' localization after a 1-h pulse of mitomycin C. For discontinuities and interchanges, 60-70% of the inferred 'break-points' were localized to defined paracentric heterochromatin and the centromeric regions (i.e. approximately 21% by length of the normal karyotype), irrespective of 'dose', aberration frequency, sample time or cycle sub-phase as determined by replication banding. Chromatid intrachanges are non-(or negatively) localized because of an inescapable scoring bias. SCE in fibroblasts show no such localization. Cells from a number of Fanconi's anaemia subjects were examined. In poorly growing cultures, localization was as high as in normal cells but in vigorous cultures localization was reduced to approximately 30%. It is suggested that the enhanced aberration sensitivity of this syndrome could arise because non-localized aberrations, usually eliminated before division in normal cells, are allowed to reach mitosis in FA cells.
D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002875:Chromosomes / Q000187:drug effects*; D004261:DNA Replication; D004305:Dose-Response Relationship, Drug; D005199:Fanconi Anemia / Q000235:genetics; D005347:Fibroblasts; D006801:Humans; D008214:Lymphocytes; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity*; D008940:Mitotic Index / Q000187:drug effects
D008937:Mitomycins; D016685:Mitomycin