Detection of radiation-induced chromosome aberrations using fluorescence in situ hybridization in drug-induced premature chromosome condensations of tumour cell lines with different radiosensitivities.
A potential assay for radiosensitivity of human tumours is that of radiation-induced chromosome damage determined on metaphase spreads of human solid tumours. It is often difficult, however, to obtain enough metaphases for cytogenetic analysis after radiation. A possible solution would be to use the technique of premature chromosome condensation (PCC), enabling the study of interphase cells. The induction of PCCs using mitotic inducer cells is technically difficult, however, and the frequency of induction relatively low. We have attempted to use another approach, to induce PCCs using the phosphatase inhibitors okadaic acid and calyculin A. Both inhibitors were found to induce PCCs in several human tumour cell lines, with calyculin A producing the higher incidence. Determination of radiation-induced chromosome aberrations using fluorescence in situ hybridization on these chemically induced PCCs showed a clear difference between a radiosensitive (SCC61) and a radioresistant (A549) tumour cell line, with more aberrations in the sensitive line. Owing to incomplete condensation compared with that in standard metaphases, accurate classification of aberration types was not possible. Despite this limitation, the present data indicate that this relatively quick and simple method may be useful for determining chromosome aberrations in interphase cells and potentially in human solid tumours for predictive assay purposes.
Coco-Martin
J M
JM
Division of Experimental Therapy, the Netherlands Cancer Institute Plesmanlaan 121, Amsterdam, Netherlands.
Begg
A C
AC
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008387:Marine Toxins; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; D019319:Okadaic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases