Zearalenone induces chromosome aberrations in mouse bone marrow: preventive effect of 17β-estradiol, progesterone and Vitamin E

The cytogenetic effect of zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, was evaluated in vivo, in mouse bone marrow cells, by assessing the percentage of cells bearing different chromosome aberrations. The studies included different conditions for animal treatment, as follows: (1) single intraperitoneal (ip) injection, (2) repeated ip injections, (3) pre-treatment for 24 h with Vitamin E (Vit E), and (4) pre-treatment for 4 h with 17β-estradiol (17β-Est) or progesterone (Prog). ZEN induced different types of chromosome aberrations, which was concentration-dependent (2–20 mg/kg bw). These doses corresponded to 0.4–4% of the LD₅₀ in the mouse. Interestingly, when the dose of ZEN (40 mg/kg) was fractionated into four equivalent doses (4 × 10 mg/kg bw), into three doses (15 + 10 + 15 mg/kg bw), or into two equivalent doses (2 × 20 mg/kg bw), given every 24 h, the percentage of chromosome aberrations increased significantly. This finding suggests that ZEN proceeds by reversible binding on receptors that could become saturated, and that it damages the chromosomes in a ‘hit and go’ manner. Furthermore, pre-treatment of animals with 17β-estradiol or progesterone significantly decreased the percentage of chromosome aberrations, suggesting that (i) these hormones bind to the same cytoplasmic receptors transported into the nucleus to elicit DNA damage, (ii) they may play a role in preventing chromosome aberrations induced by ZEN. Similarly, Vit E prevented these chromosome aberrations indicating that Vit E, previously reported to prevent most of the toxic effects induced by ZEN, may also bind to the same receptors.     

The cytogenetic and hepatotoxic effects of dioxin on mouse liver cells

The cytogenetic and hepatotoxic effects of 2,3,7,8-tetrachlorodibenzo p-dioxin (TCDD) on mouse liver cells were investigated. Male C57BL/6J strain mice, which have TCDD receptors, were given single intraperitoneal injections of 25, 37.5, 75 and 150 g of TCDD/kg body weight or corn oil carrier alone. Two-thirds hepatectomies were carried out at 1 or 7 days after injection and chromosomal aberrations and mitotic indexes of the regenerating hepatocytes were scored 54 hr after hepatectomy. Liver sections from additional intact mice were studied for TCDD-hepatotoxicity at 1, 7 and 30 days after injection. The three high doses of TCDD caused hepatotoxicity with necrosis of liver cells and focal architectural collapse by 30 days after injection. No evidence was obtained of an increase in the frequency of chromosomal structural aberrations at doses that allowed sufficient mitotic activity for cytogenetic evaluation. We conclude that TCDD is not a clastogen for mouse hepatocytes, although high doses cause marked hepatocellular necrosis.Abbreviations CSD chromosome deletion - META metacentric chromosome - TCDD 2,3,7,8-tetrachlorobenzo-p-dioxin     

Chromosome aberrations (CA), sister-chromatid exchanges (SCE) and mitogen-induced blastogenesis in cultured peripheral lymphocytes from 48 control individuals sampled 8 times over 2 years

Confidence in the measurement of positive effects determined by monitoring of environmentally or occupationally exposed individuals can be enhanced by a knowledge of the normal variability in these endpoints in the general population. Confounding effects can be determined and study interpretation improved by correlation of this variability with various lifestyle factors such as sex and age of donor, smoking and drinking habits, viral infections, exposure to diagnostic X-rays, etc.

8 blood samples were taken from each of 24 male and 24 female volunteers over a period of 2 years. Questionnaires pertaining to lifestyle were completed at the time of each sampling. Whole blood was cultured and slides prepared for CA or SCE analysis. Separated mononuclear cells were cultured with a range of phytohaemagglutinin concentrations and the maximum level of mitogen-induced blastogenesis was determined by measurement of [³H]thymidine uptake.

There was a significant effect of both year and season of sampling for all 3 endpoints. No significant effects in any of the 3 endpoints were found with respect to sex or age of donor nor any of the other lifestyle factors, although SCE frequency and mitogen-induced blastogenesis were nearly always higher in females than males. These results point to the need for concurrent sampling of controls with exposed populations.     

Chromosomal aberrations induced by cobaltous chloride in mice in vivo

The effects of cobaltous chloride in inducing chromosomal aberrations were observed on laboratory bred mice in vivo after single oral administration of different fractions (1/10, 1/20, 1/40) of the lethal toxic dose of the salt. Bone marrow cells were flushed out and processed for chromosome studies following colchicine, hypotonic, giemsa, air drying procedure. The parameters screened were chromosomal aberrations, with and without gaps and break per cell. Slides were screened after the expiry of 6, 12, 18, and 24 h. Statistical analysis indicated the clastogenic effects of the salt. The degree of chromosome damage was directly related to the concentration, and also to the period after administration. The different stages of the cell cycle were affected.     

Active Oxygen Contributes to the Major Part of Chromosomal Aberrations in V79 Chinese Hamster Cells Exposed to N-Hydroxy-2-Naphthylamine

N-hydroxy-2-naphthylamine (NOH-2NA). an active metabolite of human occupational bladder carcinogens, induced, in V79 Chinese hamster cells. chromosomal aberrations which were suppressed in the presence of catalase and/or superoxide dismutase. The induction of the aberrations was more efficient in a more basic pH in parallel with the generation of hydrogen peroxide from NOH-2NA. The possible role of the oxidation product of NOH-2NA in the induction of the aberrations is discussed.     

微核形成与细胞周期关系的初步研究 Ⅲ.丝裂霉素c诱发人淋巴细胞染色体畸变与不同周期阶段的微核形成

为了研究染色体畸变与微核形成的关系,本实验用不同浓度的丝裂霉素C(MMC,0.025—0.4μg/ml),处理人外周血淋巴细胞,观察中期染色体畸变与不同细胞周期形成的微核间的关系。获得如下主要结果:(1)MMC诱发的染色体畸变细胞率(ACF),未经培养的G_0期淋巴细胞的微核细胞率(NC-MNCF)以及培养的淋巴细胞的微核细胞率(C-MNCF),在一定剂量范围内均呈剂量依赖性增加,并可用幂回归方程描述;(2)微核形成与染色体畸变全然无关的NC-MNCF,和C-MNCF一样,与ACF呈良好的正相关;(3)用胞质分裂阻滞(CB)法,检测MMC诱发的CB-MNCF,较C-MNCF无显著提高,MNCF/ACF的比值较小,并随着MMC剂量增加从0.15左右降到0.03。所有上述结果表明,不能简单理解微核形成与染色体畸变间的关系,在分裂的细胞群体中,中期染色体畸变可能仅是微核形成的一种来源。     

Cytogenetic characteristics of a population of Chironomus riparius Meigen 1804 (Diptera, Chironomidae) from a polluted Po river station

A population of Chironomus riparius from a Po river station near Moncalieri (a trace-metal polluted station) was studied. In this population was established a great variability of band structure of polytene chromosomes as well as paracentric heterozygous inversions, deletions, deficiencies, partial breaks, diploid chromosome fragments, and changes in functional activity and appearance of heterochromatin. In arms A through F, some bands had an increased size compared to the standard chromosomic map. Some bands appeared in a heterozygous or normal homozygous state or were amplified. In all arms, many condensed stable bands appeared in the decondensed state when compared to the standard map. Asynaptic zones in arms E and G as well as heterozygous Balbiani rings and NORs were established. Very often the 4th chromosome was almost completely heteropycnotic and looded like a pompon chromosome. For the first time in this species, a high frequency of ectopic pairings of different arms was observed. Telomeric regions involved in ectopic pairings had a granular appearance, as did some centromeres. The hypothesis is advanced that such a high frequency of structural rearrangements could be correlated with genomic distribution of specific mobile elements.     

The induction of chromosomal damage and cell killing in mouse spermatogonial stem cells following combined treatments with hydroxyurea, 3-aminobenzamide and X-rays

To analyze in more detail the relation between the sensitivity of spermatogonial stem cells to killing and the induction of genetic damage, mature male mice received combined treatments with hydroxyurea (HU), 3-aminobenzamide (3-AB) and X-rays. Stem cell killing was determined using the repopulation index method and translocations were studied via spermatocyte analysis. HU was administered at 16 or at 48 h before further treatment in order to create stem cell populations with different sensitivities in whic the translocation induction and stem cell killing could be studied and compared. The sensitivities for cell death and genetic damage appeared to be strongly correlated: at 16 h after HU significantly higher values were found than at 48 h or in controls without HU pretreatment.By using 3-AB in the treatment schedules we were able to investigate whether the sensitization of stem cells towards cell death and genetic damage is the outcome of a radiation- or drug-induced G₁ delay. The effect of 3-AB was most pronounced at 16 h after HU. This confirms that at this interval a large fraction of stem cells is in G₁. Our data therefore indicate that all treatments that induce an enrichment of G₁ cells also result in a sensitization of stem cells to cell killing or the induction of mutagenic damage.     

Genotoxicity assessment of amino zinc nanoparticles in wheat (Triticum aestivum L.) as cytogenetical perspective

Nanoparticles have a positive impact in several subjects especially in agriculture, while their safety is still being debated. Numerous commercial nano pesticide, insecticides, and fertilizers products are found in the local markets without any intensely studies on the side effect of these products on plant, human as well as environmental effects. The present study aimed to evaluate the genotoxicity of commercial amino zinc nanoparticles (AZ NPs) on Triticum aestivum L. during seeds germination and root elongation using concentration ranges (50, 100, and 150 ppm) at different exposure times (8, 16 and 24 hrs). Long term exposure to AZ NPs, exhibited only slight variation in germination rates and the elongation of roots was affected by AZ NPs treatment ranged from 97.66 to 100%. Significant reduction in the mitotic index was 35.33% after 24 hrs and 150 ppm of AZ NPs, was also observed comparing with control which was 88.0%. Genotoxicity was evaluated at a cytological level in root meristems that revealed sever variations in mitotic activity, chromosomal aberrations, and micronuclei release. Results exhibited that nano amino zinc could enter effortlessly into the cells and inhibit the normal cellular function. The decrease in the emergence of chromosomal aberrations resulting from AZ NPs exposure in a dose-dependent manner was clearly indicated that AZ NPs has induced genotoxic effect on wheat root tips.     

石油化学工人的细胞遗传学研究——Ⅰ.染色体畸变的检测

对石油化工企业工人(180人)及非石化企业对照人群(180人)进行染色体畸变的检测,结果表明:(1)石化地区居民染色体畸变频率略高于非石化地区居民,但无显著性差异。(2)石化企业中,炼油厂污水处理车间和塑料厂污水处理车间工人的染色体畸变各项指标和对照组比较(除塑料厂污水处理车间工人的染色体畸变一项指标外)或与其它4个车间(苯酚丙酮、催化裂化、乙二醇和丁二烯)比较,都有显著或极显著的升高。4个车间分别和对照组比较,没有显著升高。(3)染色体畸变频率有季节变化,春秋季明显高于冬季和夏季。(4)对照个体中,不同性别、不同年龄组及吸烟与否,对染色体畸变的各项指标均无显著性差异。但在石化企业不同年龄工人染色体畸变率的比较中,大于或等于40岁的工人组,明显高于30岁以下各组。