Involvement of specific chromosomes in radiation-induced rearrangements detected by fluorescence in situ hybridization (FISH).
ABSTRACT We investigated the involvement of chromosomes in dicentrics and translocations in human peripheral blood lymphocytes exposed to X-rays in vitro. Chromosomes 2, 4, 8, 13, 15, 16, and 22 were analyzed in three cocktails of different combinations using whole chromosome probes (WCP) with the fluorescence in situ hybridization (FISH)-painting technique. The results showed overexpression of chromosomes 2, 8, and 22 in translocation, the majority being of the complete type. Chromosome 4 was underrepresented in translocation formation in both combinations, that is, 2 + 4 + 8 in cocktail I and 4 + 13 + 22 in cocktail II. Its participation in dicentric production was in good agreement with its DNA content in association with 2, 4, and 8, whereas it was underexpressed in the combination of 4 + 13 + 22. DNA-proportional involvement was noticed with chromosomes 13 and 16 in all exchange aberrations. Underexpression of chromosome 15 was observed in translocation, which is contradictory to its overexpression in dicentric formation. The participation of chromosome 22 was predominant for both translocations and dicentrics, compared with its DNA content. The overall observation of our study supports the assumption of DNA-proportional distribution of Lucas et al. However, more data are required for chromosomes 4, 8, 15, and 22 in combination with other chromosomes.
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ABSTRACT: Toxic effects of the antineoplastic drug irinotecan on human blood cells at concentrations of 9.0 microg/ml and 4.6 microg/ml were evaluated in vitro. Using the alkaline and neutral comet assay significantly increased levels of primary DNA damage in lymphocytes were detected. The induction of apoptosis/necrosis, as determined by a fluorescent assay, was also notably increased. Cytogenetic outcomes of the treatment were assessed by the analysis of structural chromosome aberrations and fluorescence in situ hybridization. A significantly higher incidence of chromatid breaks and complex quadriradials was observed. Painted chromosomes 1, 2 and 4 were equally involved in translocations, but only the chromosome 1 was involved in the formation of quadriradials. Sister chromatid exchange analysis was performed in parallel with the analysis of lymphocyte proliferation kinetics. The higher concentration of irinotecan caused almost seven-time increase, while the lower one caused a five-time increase of the basal sister chromatid exchange frequency, accompanied with significant lowering of the lymphocyte proliferation index. Using the cytokinesis-block micronucleus assay, a dose-dependent increase in micronucleus frequency along with the formation of nuclear buds and nucleoplasmic bridges was noticed. Inhibitory effects of irinotecan on enzyme acetylcholinesterase (AChE) were studied in erythrocytes. An IC(50) value of 5.0 x 10(-7) was established. Irinotecan was found to be strong inhibitor of the acetylcholine hydrolysis and to cause a continuous decrease of catalytic activity of AChE. The results obtained on a single donor may contribute to the understanding of irinotecan toxicity, but further in vitro and in vivo studies are essential in order to clarify remaining issues, especially on possible inter-individual variability in genotoxic responses to the drug.Basic & Clinical Pharmacology & Toxicology 07/2007; 100(6):403-13. · 2.12 Impact Factor