On the localization of mitomycin C-induced aberrations in normal human and Fanconi's anaemia cells

• Published in: Mutation research Vol. 178; no. 1; p. 65
• Main Authors: Savage, J R, Reddy, K S
• Format: Journal Article
• Language: English
• Published: Netherlands 01.05.1987
• Subjects: Cells, Cultured; Chromosome Aberrations; Chromosome Mapping; Chromosomes - drug effects; DNA Replication; Dose-Response Relationship, Drug; Fanconi Anemia - genetics; Fibroblasts; Humans; Lymphocytes; Mitomycin; Mitomycins - toxicity; Mitotic Index - drug effects
• ISSN: 0027-5107
• DOI: 10.1016/0027-5107(87)90087-X

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.