Aneugenic effects of some metal compounds assessed by chromosome counting in MRC-5 human cells

Development of a comprehensive test battery is necesary for the evaluation and detection of aneugenic chemicals. The chromosome couting method was use d in the present study. The aneugenic ability of cadmium choride (1.0, 2.0 and 4.0 x 10(-3) mM), cadmium sulfate (3.3, 6.7 x 10(-5) and 1.3 x 10(-4) m M), potassium dichromate (2.5, 5.0 x 10(-4) and 1.0 x 10(-3) mM) and cacodi lic acid (1.25, 2.5 and 5.0 x 10(-2) mM) were analysed using MRC-5 cells wh ich have a modal diploid number of 2 n = 46 with a spontaneous aneuploid or polyploid cells not higher than 13% and 8%, respectively. All compounds induced significant increments of aneuploid cells in relation to negative controls. The frequency of aneuploid cells increased in all tr eatments with cadmium chloride. Cadmium sulfate induced significant increme nts of aneuploid cells with the two higher doses. All the doses of potassiu m dichromate increased the frequency of aneuploid cells although to a lesse r degree than the other compounds. In these cases, differences were in the borderline of statistical significance (p < 0.05). Moreover, a low number o f cells could be analysed in treatments with the highest dose due to the de crease in the mitotic index. Results obtained are coincident with previous reports using the same method ology in the sense that induced aneuploidy was mainly evidenced by the incr ease of hypodiploid but not hyperdiploid cells. In addition, anaphase-telop hase analysis of the effects of the same doses of these metal compounds in CHO cells showed significant increments of lagging chromosomes and increase d frequencies of kinetochore positive micronuclei in MRC-5 cells. These fin dings could be considered as an indication that the main cause of unequal c hromosome separation is the failure of kinetochores to attach the spindle a pparatus either by alteration of its protein components or by the altered c hromatid separation in anaphase. (C) 2000 Elsevier Science B.V. All rights reserved.