Diphenyl ditelluride (DPDT) is a potential prototype for the development of novel biologically active molecules. Thus, it is important to evaluate the toxic effects of this compound. In the present study, we evaluated the cytotoxic, genotoxic and mutagenic properties of DPDT in Chinese hamster fibroblast (V79) cells, in strains of the yeast Saccharomyces cerevisiae both proficient and deficient in several DNA repair pathways and in Salmonella typhimurium. DPDT induced frameshift mutations in both S.typhimurium and a haploid wild-type strain of S.cerevisiae. Mutants of S.cerevisiae defective in base excision repair and recombinational repair were more sensitive to DPDT. The results of a lactate dehydrogenase leakage assay suggest that DPDT is cytotoxic to V79 cells. At cytotoxic concentrations, this compound increased thiobarbituric reactive species levels and decreased the glutathione:GSSH ratio in yeast and V79 cells. DPDT generated single- and double-strand DNA breaks in V79 cells, both with and without metabolic activation, as revealed by alkaline and neutral comet assays. Moreover, an induction of oxidative DNA base damage was indicated by a modified comet assay using formamidopyrimidine DNA glycosylase and endonuclease III. Treatment with DPDT also induced micronucleus formation in V79 cells. Pre-incubation with N-acetylcysteine reduced DPDT's oxidative, genotoxic and mutagenic effects in yeast and V79 cells. Our results suggest that the toxic and mutagenic properties of DPDT may stem from its ability to disturb the redox balance of the cell, which leads to oxidative stress and the induction of DNA damage.
SummaryWe record the occurrence of male recombination, detected in cytological preparations of testes in 2 Drosophila willistoni population samples. Comparative analysis of meiotic figures in imaginal discs of testes and the salivary gland polytene chromosomes of male third instar larvae were employed. We observed anaphase bridges, suggesting the occurrence of chiasmata and fragmented chromatids involving the second chromosomal pair and the heterozygous inversions IILF and IILDϩE segregating in the same individuals. This was observed in non-stressed larvae maintained at physiological temperature, and opens a wide field to study the factors that regulate crossing-over in natural populations of the highly polymorphic D. willistoni. We also observed what appears to be crossing-over in the tip of chromosomal arm IIL, in a sole male heterozygote for the inversion IILH of the G3 natural population. Key words Drosophila willistoni, Meiotic chromosomes, Male recombination.Male recombination is an uncommon phenomenon in Drosophila (Morgan 1912(Morgan , 1914. This absence of recombination in males is probably a consequence of mechanisms that improve the exploration of paracentric inversion polymorphism in the great majority of Drosophila species around the world. It seems to be advantageous for Drosophila to be polymorphic for paracentric inversions, since heterozygous larvae usually present high values for several fitness components (reviews in Sperlich and Pfriem 1986, Krimbas andPowell 1992). In females, the strategy used to prevent recombination between chromosomal sections involved in paracentric inversions was the dislocation of the achromatic spindle position towards one of the extremities of the oocyte (Hinton and Lucchesi 1960). This preferential orientation of the division apparatus promotes the expulsion of one nonrecombined chromatid (with the standard or the inverted order) as the first polar body, and the compulsory expulsion of the dicentric chromatid resultant of a putative recombination inside the inverted segment as the second polar body. Consequently, this results in the maintenance of a balanced chromatid as the functional nucleus of the oocyte, since the acentric fragment generated by the same recombination process will be lost in the cytoplasm.The refinement of this mechanism, accompanied by the increasing repression of male recombination in Drosophila, is certainly the result of strong selective pressures operating along the time of evolutionary diversification of these insects. Nevertheless, some Drosophila species tolerate a certain degree of recombination in males. This is the case of D. ananassae, in which crossing-over in male meiosis seems to be a common event (Kikkawa 1937, Moriwaki 1937, Matsuda et al. 1983, Goñi 1988 and genetic factors influencing this process were discovered in widespread natural populations (reviews in Matsuda et al. 1993.In D. willistoni, the highly adaptive chromosomal polymorphism for paracentric inversions
The organoselenium compound, dicholesteroyl diselenide (DCDS) is a structural analogue of diphenyl diselenide (DPDS) and may be considered as a promising antioxidant drug in vivo. Nevertheless, little is known about the toxicological properties of DCDS. In the present study we evaluated the cytotoxic, genotoxic and mutagenic properties of DCDS in Chinese hamster lung fibroblasts (V79) and in strains of the yeast Saccharomyces cerevisiae, proficient and deficient in several DNA-repair pathways. The results with V79 cells show that DCDS induced cytotoxicity, GSH depletion and elevation of lipid peroxidation at lower concentrations than did DPDS. DCDS also generated single- and double-strand DNA breaks in V79 cells, both in the presence and in the absence of metabolic activation, as revealed by alkaline and neutral comet assays. Moreover, the induction of oxidative DNA base-damage was demonstrated by means of a modified comet assay with formamidopyrimidine-DNA glycosylase and endonuclease III. Treatment with DCDS also induced micronucleus formation in V79 cells as well as point and frame-shift mutations in a haploid wild-type strain of S. cerevisiae. Yeast mutants defective in base excision-repair proteins were the most sensitive to DCDS. Pre-incubation with N-acetylcysteine reduced DCDS's oxidative, genotoxic and mutagenic effects in yeast and in V79 cells. Our findings indicate that the presence of cholesteroyl substituents in DCDS results in elevation of its cytotoxic and genotoxic potential compared with that of DPDS in yeast and in V79 cells. However, due to dose-dependent contrasting behaviour of organoselenium compounds and differences in their toxicity in in vitro and in vivo systems, further studies are needed in order to establish the non-toxic concentration range for treatment in mammals.
-A first case of polymorphism of a pericentric inversion on X-chromosome was detected in six wild populations of Drosophila willistoni from islands and the mainland of Santa Catarina State, southern Brazil. The high representativeness of this inversion, with frequencies between 10 to 42 % in samples of wild populations from Santa Catarina State, suggests that it could be adaptive and that the establishment of such polymorphism was probably due to crossing over restriction in the chromosomal region involved in the rearrangement.
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