INDUCTION AND DISTRIBUTION OF DAMAGE IN CHO-K1 AND THE X-RAY-SENSITIVE HAMSTER-CELL LINE XRS5, MEASURED BY THE CYTOCHALASIN-B-CYTOKINESIS BLOCK MICRONUCLEUS ASSAY

The micronucleus assay holds promise as a method for determining clast ogenic effects of particular agents and for examining relative sensiti vities of eukaryotic cells to such clastogens, In the following work, a detailed examination of the induction of micronuclei in radio-resist ant Chinese hamster ovary fibroblasts (CHO-K1) and the DNA double-stra nd break repair-defective daughter cell line, xrs5, was performed. Cel ls were exposed to gamma-irradiation, bleomycin, etoposide, camptothec in and the restriction endonuclease P upsilon uII. By a simplified sta tistical analysis of data, information on the expression of chromosoma l damage, the distribution of damage and the role of cell cycle effect s on damage expression was obtained from a relatively small number of cells. Ail 5 clastogens resulted in elevated levels of micronuclei in xrs5 compared to CHO-K1. An analysis of the distribution of micronucle i within treated populations revealed differences between the modes of damage. Significant deviation from the expected values indicated that expression of micronuclei does not follow an expected Poisson distrib ution, The frequencies of binucleated cells;indicated micronucleus fre quencies do not correlate with inhibition of cell cycle progression. T his work also demonstrates that caution is required in the interpretat ion of data obtained through micronucleus assays. In particular, it do es not appear possible to proscribe simple numerical values of relativ e sensitivity or clastogenicity based on the relative number of micron uclei induced alone, (C) 1997 Elsevier Science B.V.