Herbal medicine against genotoxicity of dimethoate, an insecticide, in mammalian somatic cells.

In this study, the genotoxic effects of dimethoate (DIM) were investigated with the in vitro micronucleus test in human peripheral lymphocytes. The ethanol extracts of Rosa canina and Salvia lavandulifolia were used to remove possible genotoxic effects of these substances. For this purpose, different concentrations (0.5-1-2 µg/mL) of dimethoate, DIM + RCeta and DIM + SLeta (1:1 v/v) application groups were prepared and applied to the blood culture. The obtained data were compared with the negative control group that was prepared with dimethyl sulfoxide (DMSO) as solvent and a well-known genotoxic effects of ethyl methanesulfonate (EMS) as positive control group. It was observed in lymphocyte cells that the frequency of MN considerably increased depending on the increasing dose of DIM whereas the nuclear division index (NBI)decreased according to the control group, especially in the last concentration (2 µg/mL). But, as the MN frequency decreased, NBI values approached to control group with 2µg/mL DIM + RCeta and 2µg/mL DIM + SLeta according to DIM application group (P < 0.05). Additionally, RCeta and SLeta were analyzed by gas chromotography-mass spectrometry (GC-MS).

The relationship of micronucleus frequency and nuclear division index with coronary artery disease SYNTAX and Gensini scores.

OBJECTIVE: We aimed to evaluate the relationship of micronucleus (MN) frequency and nuclear division index (NDI) with SYNTAX and Gensini scores and thrombolysis in myocardial infarction (TIMI) frame counts of coronary arteries in patients undergoing coronary angiography. METHODS: In a single-center prospective observational study, a total of 63 individuals, 48 consecutive patients with coronary artery disease (CAD) and 15 healthy people were included. Before coronary angiography (exposure to X-ray), blood samples were collected for lymphocyte cultures, MN and NDI measurements. According to the SYNTAX and Gensini scores, patients were allocated into two groups. Group 1 and 2 included the patients with SYNTAX scores <22 and ≥22 points, respectively. Similarly, groups according to Gensini scores included the ones <23 and ≥23 points. MN test was used for in vitro studies in human peripheral lymphocytes. Binucleated lymphocytes were calculated for each patient. RESULTS: MN frequency was significantly higher in group 2 than group 1 and in group 1 than control group (p<0.001). NDI was significantly higher in control group than group 1 and in group 1 than group 2 (p=0.003). MN frequency had positive but moderate correlation with SYNTAX and Gensini scores and TFCs of left anterior descending (LAD), circumflex and right coronary arteries (r=0.394, p=0.003; r=0.458, p<0.001; r=0.425, p<0.001; r=0.469, p<0.001; and r=0.475, p<0.001, respectively). CONCLUSION: We can conclude that as the degree of atherosclerosis increases and coronary flow worsens, MN frequency increases and NDI decreases. Our results may help to elucidate the relationship of DNA damage in pathophysiology of atherosclerosis and endothelial dysfunction in patients with stable CAD.

The use of endemic Iranian plant, Echium amoenum, against the ethyl methanesulfonate and the recovery of mutagenic effects.

In this study, potential genotoxic effects of ethyl methanesulfonate (EMS) that caused mutagenicity in a variety of organisms were tried to resolve by the methanol and chloroform extract of Echium amoenum (EAmet and EAchl) Fisch. & C.A. Mey. from the family of Boraginaceae, which is an endemic plant, and is used as an alternative treatment among public in Iran. Somatic mutation and recombination test with Drosophila wing was used to determine the genotoxic and antigenotoxic effects in our investigations. For this purpose, 3-day-old transheterozygous larvae of mwh/flr(3) genotype of Drosophila melanogaster were used in all our experiments. The larvae were fed chronically on the Drosophila instant medium (DIM) including 1 ppm EMS. However, in another application group, different concentrations (1, 2 and 4 ppm) of EAmet and EAchl were added to DIM including 1 ppm EMS (EMS + EAmet and EMS + EAchl). Then, for the matured individuals, wing preparates were prepared within the mediums that include control group that has only DIM, negative control group that contains dimethyl sulfoxide and application groups in different concentrations that contain EMS, EMS + EAmet and EMS + EAchl. Clone induction frequency for the normal wing phenotype of EMS application group was observed to be 2.00. In the EMS + EAmet application group, the value of 1 ppm EAmet is 1.49, value of 2 ppm EAmet is 1.08 and value of 4 ppm EAmet is 0.72; in the EMS + EAchl application group, the value of 1 ppm is EAchl 1.33, value of 2 ppm EAchl is 0.67 and value of 4 ppm EAchl is 0.56 were determined. This decrease observed between EMS and all application groups in terms of total induction frequency is statistically significant (p < 0.05). These results concluded that chloroform extracts were more effective than the methanol extracts of E. amoenum.

Assessment of genotoxic potential of two mycotoxins in the wing spot test of Drosophila melanogaster.

Mycotoxins, the toxic products of molds, exposure causes serious adverse health problems in human, animals, and crops. Determining the potential genotoxic effects of these substances is, therefore, of great importance. We have evaluated the genotoxic toxicity of two trichothecenes--diacetoxyscirpenol (DAS) and T-2 toxin--using the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster. The SMART is based on the principle that the loss of heterozygosis of recessive markers located on the left arm of chromosome 3--multiple wing hairs (mwh) at the map position 0.3 and flare-3 (flr3) at the map position 38.8--may occur through various mechanisms such as mitotic recombination, mutation, deletion, half-translocation, chromosome loss, and nondisjunction. Both the mycotoxins were administered to third instar larvae (72 ± 4 h old) at concentrations ranging from 5 to 40 µM. Based on our results, DAS and T-2 toxins does not exert genotoxic effects up to a concentration of 40 µM.

Genotoxic evaluation of two oral antidiabetic agents in the Drosophila wing spot test.

In this study, two sulfonylureas--glimepiride and glipizide--commonly used in type 2 diabetes mellitus were investigated for genotoxicity in the Drosophila wing spot test. For this purpose, three-day-old transheterozygous larvae were treated with three mutagenic compounds, and the results obtained were compared with the control group. Mutational or recombinogenic changes were recorded in two recessive genes--multiple wing hairs (mwh) and flare (flr (3)). Two recessive markers were located on the left arm of chromosome 3, mwh in map position 0.3, and flare-3 (flr3) at 38.8, while the centromere was located in position 47.7. Wing spot tests are targeted on the loss of heterozygosity, which may be grounded in different genetic mechanisms such as mutation, mitotic recombination, deletion, half-translocation, chromosome loss, or nondisjunction. Genetic changes formatting in somatic cells of the imaginal discs cause nascence different mutant cloning in different body parts of adult flies. Our in vivo experiments demonstrated that glimepiride and glipizide show the genotoxicity, which is especially dependent on homologous somatic recombination.

Genotoxic evaluation of selective serotonin-reuptake inhibitors by use of the somatic mutation and recombination test in Drosophila melanogaster.

This study evaluated different concentrations of selective serotonin-reuptake inhibitors (citalopram and sertraline) for genotoxicity by use of the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Three-day-old larvae, trans-heterozygous for the multiple wing hairs (mwh) and flare (flr³) genes were treated with these two compounds. Two recessive markers were located on the left arm of chromosome 3, i.e. 'multiple wing hairs' (mwh) in map position 0.3 and 'flare-3' (flr³) at 38.8, while the centromere was located in position 47.7. SMART is based on the loss of heterozygosity, which may occur through various mechanisms, such as mitotic recombination, mutation, deletion, half-translocation, chromosome loss, and non-disjunction. Genetic changes occurring in somatic cells of the wing's imaginal discs, cause the formation of mutant clones on the wing blade. The results of this study show that citalopram had a genotoxic effect in the Drosophila SMART. Sertraline, however, did not show any genotoxic effect in balancer heterozygous wings. This study concluded that more information is needed to be certain regarding the mutagenic effects of sertraline.