Biomedical subjects
D Vlastos
Publications and source records attributed to D Vlastos.
Micronucleus induction in somatic cells of mice as evaluated after 1,3-butadiene inhalation.
The effect of different 1,3-butadiene (BD) inhalation doses, 130, 250, and 500 ppm, on somatic cells of mice was studied. Two different cell populations with diverse replicative and differentiative activities, namely splenocytes and peripheral blood reticulocytes, were examined and micronucleus (MN) frequencies were estimated. In splenocytes, different postinhalation time intervals were studied with regard to MN induction and characterisation. BD was found to be clastogenic by inducing increased micronucleus frequencies in both cell compartments and also to induce cytotoxicity at the highest level of exposure. In mouse splenocytes, BD has also shown a weak aneugenic effect at a short time interval after the exposure. Postinhalation time influences the induction of chromosome damage in stimulated splenocytes treated in vivo, since MN frequency decreases with time; in addition, BD has shown its aneugenic and cytotoxic potential only at 2 days after exposure.
Effects of cetirizine dihydrochloride on human lymphocytes in vitro: micronucleus induction. Evaluation of clastogenic and aneugenic potential using CREST and FISH assays.
Cetirizine dihydrocloride, a widely administered antiallergic drug with the amine piperazine in its molecule, was studied as to its ability to cause micronucleus formation in human lymphocyte cultures treated in vitro. Peripheral lymphocytes from four different donors were cultured and treated with different concentrations of the compound. Cetirizine dihydrocloride was shown to induce enhanced micronucleus frequency in a dose-dependent manner, although lymphocytes from the different donors showed different susceptibilities to the compound. The content of induced micronuclei was investigated in one of the four donors by two independent assays, CREST (the application of antikinetochore antibodies) and FISH (fluorescence in situ hybridization) on cytochalasin B-formed binucleated cells. It was shown that the induced micronuclei resulted from breakage events as well as chromosome loss, thus characterizing cetirizine dihydrocloride as both clastogen and aneugen. Since our results were derived only from in vitro experiments, we believe that an extensive in vivo study is necessary before drawing conclusions as to the effects of cetirizine dihydrochloride in patients.
Induction of micronuclei and sister chromatid exchange in mouse splenocytes after exposure to the butadiene metabolite 3,4-epoxy-1-butene.
3,4-Epoxy-1-butene (EB) is one of the main metabolites of 1,3 butadiene, a widely used industrial chemical. The mutagenic potential of 1,3 butadiene and its metabolites have been studied in different test systems. In this work the genotoxic effects of EB were studied by estimating micronuclei (MN) and sister chromatid exchange (SCE) frequencies in stimulated mouse splenocytes. Mice were treated in vivo with various doses of EB (24.4, 48.8 and 73.2 mg/kg). The antikinetochore antibody technique (CREST) was also applied to MN in cytokinesis blocked cells to investigate any possible aneugenic effect. Both MN and SCE frequencies increased after EB treatment. The induced MN resulted mainly from acentric fragments but a weak aneugenic effect was found as well. Cytotoxic effects of EB were observed at the highest dose. The above results, in combination with others on the effect of 1,3 butadiene and its metabolites in somatic and germ cells of mouse and rat as well as in somatic human cells, form a part of the information needed for application of the parallelogram approach and extrapolation to human risk.
A comparative study on the effect of MNU on human lymphocyte cultures in vitro evaluated by O6-mdG formation, micronuclei and sister chromatid exchanges induction.
N-Nitroso-compounds are a large group of chemicals present in a number of environmental sources and many of them are mutagens as well as carcinogens in experimental animals. Among the known N-nitroso-compounds, N-nitroso-N-methylurea (MNU) is a strong mutagen. In this study an effort has been made to compare the ability of MNU to methylate the O6-guanosine site in DNA and to induce micronuclei and sister chromatid exchanges in human lymphocyte cultures in vitro. To quantitate O6-methyldeoxyguanosine (O6-mdG) a highly sensitive immunoassay, immuno-slot-blot (ISB), has been used. For the evaluation of micro nuclei (MN) the cytokinesis block micronucleus method has been used. Different concentrations (75, 100, 125 micrograms/ml) were tested. At the highest concentration tested for the MN induction, 125 micrograms/ml, the occurrence of binucleates and micro nuclei is higher than twice in relation to control and a reduction in NDI is also observed. The same concentrations were used for the estimation of sister chromatid exchanges (SCEs) induction. The mean number of SCEs at 125 micrograms/ml is almost three times that of the control level. The concentrations tested for the quantitation of O6-mdG were 200, 300 and 400 micrograms/ml and this was done because for the test system we used and for the given experimental conditions the first indication of O6-mdG formation was at 200 micrograms/ml. Our results show that methylation of O6-guanosine increases with concentration and at 400 micrograms/ml the concentration of O6-mdG is 5.83 fmol/microgram DNA, while at the control level it is 2.40 fmol/microgram DNA. Since O6-mdG formation is observed in higher concentrations than those of MN and SCE induction it would be interpreted that O6-mdG levels are not correlated with the studied cytogenetic effects although one has to take into consideration the total promutagenic lesions in DNA, induced by MNU, as well as AGT repair activity.
Effects of cetirizine dihydrochloride on human lymphocytes in vitro: evaluation of chromosome aberrations and sister chromatid exchanges.
The ability of cetirizine dihydrochloride, an antihistaminic agent, to induce chromosome aberrations as well as sister chromatid exchanges (SCEs) was evaluated in human lymphocyte cultures treated in vitro. The following concentrations were tested: 25, 50, 75, 100 and 200 micrograms/ml. The results of our study revealed that cetirizine dihydrochloride is capable of inducing chromosome aberrations, at least at the higher concentrations studied, 100 and 200 micrograms/ml. The majority of aberrations was of chromatid type. Cetirizine is also a weak inducer of SCEs. Further studies are now warranted in order to define the in vivo cytogenetic activity of cetirizine in humans.