D. Vlastos, G. Stephanou
Apr 9, 1999
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Quality indicators
Journal
Archives of Dermatological Research
Abstract
With regard to Dr. Roba’s (Head Product Safety and Metabolism, UCB) letter concerning our report of the effects of citirizine on micronucleus induction in human lymphocytes [1], we would like to make the following comments. Our experiments were carried out using the specific batch of cetirizine from UCB that is mentioned in our report which was also used for the evaluation of chromosome aberration and sister chromatid exchange frequency in a previous study [2]. Peripheral lymphocytes from four different donors were cultured and treated with different concentrations (25–200 μg/ml) of cetirizine dihydrochloride in order to evaluate the ability of the compound to induce micronucleus formation. Lymphocyte cultures as well as cytogenetic analysis were carried out according to previously published internationally recognized recommendations that have been applied in our laboratory since 1983 for the study of the effects of environmental chemicals, including pharmaceutical compounds, in collaboration with other European laboratories. A total of 11000 binucleated cells were analysed for each experimental point. It was shown that the drug induced enhanced micronucleus frequencies in every tested donor and in a dose-dependent manner. A different donor susceptibility was observed in relation to the concentration level at which a positive response first appeared, and for this reason the results were not pooled. This is an intriguing point that may indicate a personal sensitivity to the drug. Furthermore, in different experiments, it was shown by CREST (application of antikinetochore antibodies) and FISH (fluorescence in situ hybridization) analysis that the induced micronuclei, at least at the highest concentrations tested (100 and 200 μg/ml), resulted from breakage events as well as from chromosome loss. In addition cetirizine dihydrochloride was also found to increase chromosome aberration and sister chromatid exchange frequency in cultures of lymphocytes from the same donors [2], the results being in accordance with the observed micronucleus induction. Nowhere in our reports, a concern for the safety of the drug is mentioned. In our opinion our results are interesting and may provoke further research on the effects of cetirizine in humans, given the contradictory data cited by Dr. Roba, the detailed results of which would be of interest to the international scientific community. We do believe that an extensive in vivo study is necessary before any conclusion can be drawn as to the effect of the drug on patients, and to our knowledge such a study has not yet been carried out and reported.