The genotoxic effect of gunshot wounds

Evidence for alterations in chromosomes of experimental animals (rats) and humans after gunshot wounds is presented. The rate of chromatid exchanges induced by gunshot wounds in humans depend on the saturation of body tissues with ascorbic acid. It is assumed that free-radical processes underlie the deleterious effect of gunshot wounds on chromosomes.     

The genotoxic effect of beta-propiolactone on mammalian oocytes

beta-Propiolactone (beta PL) has been tested on preimplantation mouse embryos for possible genotoxic effects. Tests were performed at different stages of meiosis (late prophase I, diakinesis/metaphase I, anaphase I, telophase I/prophase II and metaphase II) by injecting females at various times after the induction of superovulation. Male and female derived chromosome complements from first-cleavage embryos were analysed before syngamy for cytogenetic abnormalities. A higher proportion of diploid oocytes, produced by the non-extrusion of the first or second polar body, was found after fertilization when the compound was administered immediately before metaphase I or II. No obvious effect was detected at any other time of beta PL exposure. Based on these results, several possible modes of action for beta PL are postulated.     

Gamma-decanolactone effect on behavioral and genotoxic parameters

Gamma-decanolactone is a monoterpene compound, which is shown to be active in some animal models. The psychopharmacological evaluation of this compound in mice has revealed that it has a dose-dependent effect on the central nervous system, including hypnotic, anticonvulsant and hypothermic activities. The aim of the present study was to evaluate the effect of gamma-decanolactone at 0.1 and 0.3 g/kg on behavior parameters related to plus-maze, open field and forced swim tests. In addition, we investigated its genotoxic activity. Gamma-decanolactone at the dose of 0.3 g/kg, but not 0.1 g/kg, decreased the number of crossings and rearings and there were no significant differences among groups regarding the latency to start locomotion in open field. A single i.p. administration of gamma-decanolactone, at the higher, but not at lower dose used, was able to increase the exploratory activity in the test session (24 h after training), as assessed by the number of rearings performed in open field, and induced DNA damage on brain tissue as measured in comet assay, suggesting an impairment of nonassociative, nonaversive learning and a genotoxic effect on CNS. Gamma-decanolactone did not change the behavior of animals in plus-maze and forced swim tests, suggesting this compound shows no anxiolytic or antidepressant activity.     

Bacterial pigment prodigiosin and its genotoxic effect

A pigment complex has been isolated from the biomass of bacteria Serratia marcescens ATCC 9986 and separated into single fractions by chromatography. An analysis of the fractions by spectrophotometry, thin layer chromatography, NMR spectroscopy and mass spectrometry enabled us to isolate the so-called red fraction, to confirm the identity of the product of the red fraction to the pigment prodigiosin, and to prove its purity. Some features of the toxic action of prodigiosin have been revealed. It has been found for the first time that the pigment is capable of inducing mutations in Salmonella typhimurium TA 100 cells (Ames test) and chromosomal damage in mammalian erythroblasts.     

An adherent mucus layer attenuates the genotoxic effect of colibactin

The human gastrointestinal tract is a complex ecosystem in which epithelial cells and microorganisms of the intestinal microbiota live in symbiosis. Certain members of the microbiota, in particular Escherichia coli strains of the B2 phylotype, carry the polyketide synthase‐island encoding the genotoxin colibactin. Colibactin is a nonribosomal peptide or polyketide‐nonribosomal peptide hybrid of still unsolved structure, which induces DNA double strand breaks (DSBs) in eukaryotic cells. However, direct contact between live bacteria and host cell is required in order to elicit these genotoxic effects. In this study, we used a variety of cell culture models, among them, a 3D cell culture approach based on decellularised small intestinal submucosa, to investigate whether the intestinal mucus layer has the potential to interfere with colibactin activity. We demonstrate that the expression of mucins and the formation of an adherent mucus layer significantly increased with increasing complexity of cell culture. Moreover, we show that the presence of an adherent mucus layer on epithelial cells attenuates the genotoxic activity of colibactin, by preventing the induction of DNA‐DSBs. Removal of the adherent mucus layer restored the occurrence of DNA‐DSBs.     

The genotoxic effects of 2,4,5-T

2,4,5-T (2,4,5-trichlorophenoxyacetic acid) is a herbicide that is used primarily for brush and weed control on rangelands and pastures, and rights-of-way. Commercial formulations contain up to 0.1 ppm of the contaminant dioxin (TCDD) which has been shown to cause birth defects and tumors in animals when administered in concentrations below 100 ppt. In many studies (especially in literature prior to 1970) it is not clear whether the reported genotoxic effects are the result of the 2,4,5-T per se, the TCDD contaminant, or a combination of both.The possible harmful effects of 2,4,5-T to humans and wildlife came into prominence during the Vietnam war when the American Army used Agent Orange (equal parts of 2,4-D and 2,4,5-T) for defoliation purposes. The reported increases in the incidence of congenital malformations and certain types of cancer in defoliant-treated regions led to the Bionetics Research Laboratory study in which 2,4,5-T was reported to cause developmental abnormalities in rats.Subsequent research showed that 2,4,5-T is a clastogen producing chromosome aberrations including bridges and micronuclei in a variety of animal and plant species. In addition, 2,4,5-T induces cell enlargement, lengthens the duration of the mitotic cycle, extends DNA synthesis, induces mitosis and causes chromosome contraction, stickiness, and sticky bridges, all at low concentrations. C-Mitoses, multinucleate cells, polyploidy, reduced fertility, and species resistance have also been reported. In vivo production of chromosome aberrations in humans is inconclusive. The emulsifiers and solvents in commercial preparations of 2,4,5-T have also been shown to induce chromosome aberrations. 2,4,5-T is only weakly mutagenic with positive reports recorded in only 2 of 4 sex-linked lethal tests in Drosophila and in one of two studies on Saccharomyces cerevisiae. Only two studies on carcinogenicity from 2,4,5-T are reported with contradictory results. While the data on teratogenicity are not clear-cut, the number of positive reports suggest that 2,4,5-T is definitely teratogenic both with and without TCDD and that 2,4,5-T and TCDD may potentiate teratogenic activity. Further studies, including epidemiological investigations of human groups exposed to 2,4,5-T, are required to supplement insufficient data and to resolve contradictory evidence.     

A new method to reveal the genotoxic effects of N-nitrosodimethylamine in pregnant mice

DNA damage and repair in kidney and liver of mouse fetuses exposed to selected doses of N-nitrosodimethylamine (NDMA) (CAS No. 62.75.9) were studied using the alkaline elution technique. CD1 female mice (15 days pregnant) were treated i.p. with 2 and 10 mg/kg b.w. of NDMA; a slight increase in DNA damage was observed in their fetuses compared to untreated controls. A 2-fold higher extent of DNA damage was induced when mice were treated by intrafetal injections of a rat S9 activating fraction (S9) immediately before exposure to the same dose of NDMA by transplacental means. The DNA-strand breaks disappeared as a function of time in animals treated with NDMA alone. In contrast, a significant persistence of DNA damage was detected in the liver and lung of fetuses which were treated with S9 and NDMA in sequence. These experiments demonstrate the metabolic immaturity of unborn mice as far as the carcinogenic activation of NDMA is concerned and show the high susceptibility of fetal tissues to DNA-damaging agents. The alkaline elution applied in vivo by the transplacental route combined with the intrafetal injection of an exogenous activating microsomal fraction allow to extend our knowledge on the interaction of metabolism-dependent chemicals with fetal tissues.     

Genotoxicity and genotoxic enhancing effect of tetrandrine in Salmonella typhimurium

Tetrandrine has been used for the treatment of silicosis in China. The potential genotoxic and carcinogenic hazards of this drug were studied using the Salmonella/histidine reversion assay and the SOS/Umu test. The results show that tetrandrine was weakly mutagenic to Salmonella typhimurium TA98 with metabolic activation and did not induce SOS response. However, tetrandrine increased the mutagenic activity of benzo[alpha]pyrene, trinitrofluorenone (TNF), 2-aminoanthracene (2AA), diesel emission particles, airborne particles, and cigarette smoke condensate by more than 100%; the activity of aflatoxin B1 and fried beef was increased by over 75%. It also increased the 2AA and TNF-induced SOS response by more than 300%. These results indicated that tetrandrine was a weak promutagen inducing frameshift mutations and was a potent genotoxic enhancer. The mechanism for the genotoxic enhancement is not known. However, the fact that the increase in mutagenicity was noted only in TA98 and not in TA1538 suggested that the enhancement of genotoxicity by tetrandrine may result from an increase in error-prone DNA repair.     

SAR modeling of genotoxic phenomena: the effect of supplementation with physiological chemicals

Structure-activity relationship (SAR) modeling of toxicological phenomena is optimal when the ratio of toxicants to non-toxicants included in the model is unity. Frequently, however, the experimental data available are enriched with toxicants, this appears to be especially true for genotoxicity data sets. It is demonstrated herein, using a Salmonella mutagenicity data set, that when there is a paucity of non-toxicants, the learning set may be augmented with physiological chemicals on the assumption that they are non-genotoxic.     

The apoptotic,cytotoxic and genotoxic effect of novel binuclear boron-fluoride complex on endometrial cancer

Endometrial cancer (EC) is one of the most common types of gynecologic cancer of the female genital tract; it considered being the fourth leading death factor among other types of cancer. Therefore, developing new anti-cancer agents are crucial for cancer treatment. Based on the potential of Schiff based complexes for the induction of apoptosis, Schiff base compounds, and their metal complexes displayed excellent anticancer properties. In this current study, antiproliferative activity of [L(BF₂)₂] as a novel binuclear boron-fluoride complex was examined to preliminary research in eight different cell lines, HELA, DU-145, PC3, DLD-1, ECC-1, PNT1-A, HT-29, and MCF-7, it was found to have a potent, suppressive effect on human endometrial adenocarcinoma cell line ECC-1. Based on this data, later investigated its apoptotic, cytotoxic, and genotoxic properties on human endometrial adenocarcinoma cell line ECC-1 in different concentrations. Apoptotic and cytotoxic tests such as single cell gel electrophoresis assay (comet assay), DNA fragmentation laddering, acridine orange test for DNA damage, and ELISA for apoptotic measurement was performed. We also gauged the oxidative status by evaluating total antioxidant status (TAS) and total oxidant status (TOS). Oxidative stress index (OSI) was calculated too. As a result [L(BF₂)₂] has been found to have a marvelous effect on ECC-1 cells, especially in damaging their DNA and cause a series of reactions lead to apoptosis. Taken together, it suggests that the [L(BF₂)₂] complex can induce the apoptotic pathway of endometrial cancer cells and is a possible candidate for future cancer treatment studies.     

朱砂叶螨抗药性监测

本文采用药膜法建立了朱砂叶螨Tetranychus cinnabarinus（Boisduval）对5种杀螨剂的敏感基线,并对6个不同地理种群的朱砂叶螨进行了抗药性监测,结果表明：5种药剂杀螨活性由高到低分别为阿维菌素〉丁氟螨酯〉氧化乐果〉炔螨特〉甲氰菊酯,其对朱砂叶螨雌成螨的LC50值分别为0.08、2.19、67.89、201.19和605.27mg/L;朱砂叶螨各地理种群已对甲氰菊酯和炔螨特产生了低、中水平的抗性,其抗性倍数分别介于2.93～16.22与4.85～14.35之间,其中云南种群对这2种杀螨剂抗性最高,对氧化乐果与丁氟螨酯处于敏感性降低阶段,其抗性倍数分别介于2.35～4.26与1.56～2.11之间,对阿维菌素还未产生明显抗性;对阿维菌素和甲氰菊酯的增效剂生物测定结果表明,三类解毒酶系（多功能氧化酶、谷胱甘肽S-转移酶和酯酶）都不同程度地参与了朱砂叶螨抗药性的形成。     

The evaluation of protective effect of lycopene against genotoxic influence of X-irradiation in human blood lymphocytes

Many studies suggest that exogenous antioxidants may protect cells against DNA damage caused with ionizing radiation. One of the most powerful antioxidants is lycopene (LYC), a carotenoid derived from tomatoes. The aim of this study was to investigate, using the comet assay, whether LYC can act as protectors/modifiers and prevent DNA damage induced in human blood lymphocytes, as well as to mitigate the effects of radiation exposure. In this project, LYC, dissolved in DMSO at a concentration of 10, 20 or 40 μM/ml of cell suspension, was added to the isolated lymphocytes from human blood at appropriate intervals before or after the X-irradiation at doses of 0.5, 1 and 2 Gy. Cell viability in all groups was maintained at above 70%. The results showed the decrease of DNA damage in cells treated with various concentrations of LYC directly and 1 h before exposure to X-rays compared to the control group exposed to irradiation alone. Contrary results were observed in cells exposed to LYC immediately after exposure to ionizing radiation. The studies confirmed the protective effect of LYC against DNA damage induced by ionizing radiation, but after irradiation the carotenoid did not stimulate of DNA repair and cannot act as modifier. However, supplementation with LYC, especially at lower doses, may be useful in protection from radiation-induced oxidative damage.     

The genotoxic potential of bases and nucleosides

This study was conducted to determine if naturally occurring cell constituents could themselves cause mutation. All the bases and their corresponding nucleosides have been shown to produce chromosome damage in P338 mouse lymphoma and Chinese hamster ovary cells in culture. In addition thymidine has produced an increase in V79 cells resistant to 8-azaguanine and ouabain. Such damage probably arises as a result of imbalanced DNA-precursor pools. Thus mutagenic events may arise by mechanisms unrelated to direct alterations of DNA.     

The mechanisms of the manifestation of the genotoxic effects of binase]

The high concentrations of commercial sample of Bacillus intermedius 7P ribonuclease (binase) showed a weak mutagenic effect in Ames test and Ara-test. It has been established that binase induces the SOS-functions of microbial cell and prophage induction. The way of exogenic enzyme action through activation of RecA protein is proposed.     

Selection of solvents for topical application acaricide testing

Investigation of a range of solvents for topical application acaricide tests on mites indicated that the choice was limited by solvent power, viscosity and toxicity. Acetophenone and anisole proved useful solvents but acetophenone appeared to have poor wetting power which caused variability in acaricide LD₅₀ levels compared with other solvents when tested on Tetranychus urticae.

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Résumé La recherche d'une gamme de solvants pour les essais d'acaricide sur acariens par application locale a montré que le choix est limité par le pouvoir dissolvant, la viscosité et la toxicité.L'acétophénone et l'anisole se sont révelés des solvants utilisable mais l'acétophénone est apparue avoir un faible pouvoir mouillant qui provoque une variabilité dans les valeurs de la DL₅₀ de l'acaricide par rapport à d'autres solvants dans les essais sur Tetranychus urticae Koch.

     

The infectivity of Schistosoma mansoni in mice, following dipping with an acaricide

The effect of prior treatment of mice with an acaricide (Alugan) on the infectivity of Schistosoma mansoni cercariae via the percutaneous route was assessed. No effects were observed, even in animals dipped only 1 day before exposure to cercariae.