Chromosome Aberrations In Spermatocytes Research Articles

Genotoxicity, DNA damage and sperm defects induced by vinblastine

BackgroundThe treatment with chemotherapy may develop secondary tumors as a result of chemo genotoxicity. Sperm defects is another complication associated with chemo treatment. In this study the genotoxicity of vinblastine (VB) was estimated in both somatic and germ cells.Materials85 mice were taken. Four single doses of VB at 3, 4.5, 6 and 10 mg/kg and three successive doses at 3, 4.5 and 6 mg/kg were taken for estimation of chromosomal aberrations (CAs). Four single doses of VB were involved in estimating the DNA fragmentation, and comet assay. For sperm abnormalities mice were injected with three successive doses of VB at 3, 4.5, and 6 mg/kg.ResultsThe results demonstrated a significant frequency of DNA fragmentation in spleen cells and in the percentage of CAs in bone marrow. Numerical and structural aberrations were recorded with a pronounced number of polyploidy metaphases which reached (11.60%) after treatment with 6 mg/kg for three successive days vs zero for control. VB also induced a significant percentage of CAs in spermatocytes in the form of univalent. Sperm defects in the form of coiled tail, absence of acrosome and shapeless head and a significant DNA damage in the testes were recorded. The frequency of sperm abnormalities reached 11.06 ± 0.14 after treatment with highest tested dose (6 mg/kg) vs 3.04 ± 0.19 for control.ConclusionVB is genotoxic in somatic and germ cells. Sperm defects induced by VB are of serious concern to future generations and may affect the fertility of cancer survivors.

Inhibitory activity of black mulberry (Morus nigra) extract against testicular, liver and kidney toxicity induced by paracetamol in mice.

Black mulberry (Morus nigra) leaves is broadly used in traditional medicine worldwide. However, there are no scientific reports regarding testicular protection, hepato-and nephroprotective activities of M. nigra leaves. The present investigation wasassessed the protective mechanism by which methanol extract from M. nigra leaves suppressed the damaging effects induced by paracetamol (APAP) in different mouse tissues. Male mice were orally given APAP (500mg/kg) with or without M. nigra extract (150, 300, and 500mg/kg) for four consecutive days. The results showed that crude extract possessed potent antioxidant activity (EC50 = 42.97µg extract/mL) due to the presence of a high amount of polyphenol and flavonoid compounds. Gallic acid, chlorogenic acid, catechin, and rutin were isolated from the n-butanol fraction of M. nigra extract. Unexpectedly, oral administration of APAP did not induce chromosomal aberrations in mouse bone marrow; however, it produced damaging effects on testis, liver, and kidney tissues. Interestingly, M. nigra extract suppressed APAP-induced genotoxicity by lowering meiotic chromosomal aberrations in spermatocytes, morphological sperm abnormalities, and % DNA damage in comet tail in the liver and kidney tissues. The altered levels of glutathione S transferase activity, lipid peroxidation, liver, and kidney functions were significantly reversed when M. nigra was given to APAP group. The restoring of the histo-architectural distortions and decreasing over-expression of p53 protein as determined by immunohistochemistry in the liver, kidney, and testis sectionswere strengthened the protective activity of M. nigra extract. Conclusion, the bioactive components in the leaves of black mulberry appear to be a good candidate for genetic protection, treatment of oxidative stress-induced organotoxicity.

Protective Effect of Vitamin C on Trimethyltin Induced DNA Damage Using Comet Assay and Chromosomal Aberrations

The objective of this study is to investigate the utility of comet assay and chromosome aberrations analysis for detecting the possible antimutagenic activity of vitamin C to reduce the genotoxic effect of Trimethyltin (TMT). TMT is one of the organotin compounds which is widely used as polyvinyl chloride heat stabilizers and marine biocides. In this study, male Swiss mice were treated interapretoneally (i.p.) with 3 tested doses 0.25, 0.50 and 1.0 mg TMT/kg b.wt. for 1, 2 and 3 d. Alkaline comet assay in nucleated bone-marrow cells and chromosome analysis in spermatocytes were performed 24 h after the last treatment. The amount of DNA damage in cells was estimated from comet tail length as the extent of migration of the genetic material. A significant increase in comet tail length indicating DNA damage was observed at all concentrations compared with control (p<0.05). The mean comet tail length showed a concentration-related and time-dependent increase. Also, the percentage of chromosome aberrations in spermatocytes was statistically significant (p<0.05) and showed dose and time dependent manner. Concurrent administration of vitamin C (VC) orally at 20 mg/kg b.wt. with the highest dose of TMT for 1, 2 and 3 d reduced DNA damage in somatic and germ cells to a significant extent. In conclusion, our results indicated that vitamin C ameliorated DNA damage and genotoxicity induced by trimethyltin in mice somatic and germ cells in vivo.

Inhibition of mitomycin C-induced chromosomal aberrations by micrometer powder of selenium-enriched green tea in mice spermatocytes

The anticlastogenic effect of micrometer powder of selenium-enriched green tea (MSTP) was evaluated by using a chromosomal aberration assay in mouse testicular cells. Animals fed with a Se-deficient diet were treated with MSTP, micrometer powder of regular green tea (MRTP), selenite, and MRTP + selenite for 30 days by an intragastric route, followed by treatment of mitomycin C (MMC) on day 19 through intraperitoneal injection (ip). Selenium status and antioxidant enzymes were measured. Results indicated that MSTP showed a significant capability to reduce the incidence of MMC-induced chromosomal aberrations in spermatocytes from 22.7% to 6.7%. This inhibitory was highest, for MSTP, at 73.1%, while it was only 38.4% for MRTP. After 30 days of a Se-deficient diet, mice, either with or without the MMC treatment, showed a lower selenium concentration in blood and liver as well as lower enzyme activity of the antioxidants, GPx and SOD. Supplementation with MSTP, selenite, or selenite + MRTP enhanced the activities of these antioxidant enzymes. This enhancement was accompanied with a concomitant elevation of selenium levels, which favored the synthesis of the seleno-enzyme GPx and protected the cells from the MMC-induced oxidative stress. Our results indicate that MSTP is both able to prevent the chromosomal aberrations induced by MMC in mouse spermatocytes and to enhance GPx and SOD activity in blood serum and liver.

Cytogenetic Studies on Two Drugs for Natural Relief of Prostatic Disorders

Pepon and prostoplex, new drugs containing natural substances, are used in the treatment of prostatic disorders. The cytogenetic effects of these drugs were tested in mice's bone marrow and spermatocytes cells at two doses comparable to propose human therapeutic and double therapeutic doses.The results revealed that the total numbers of structural chromosomal aberrations in mice's bone marrow, with or without gap, were significantly increased at p<0.01 for pepon and at p<0.05 for prostoplex at therapeutic doses. Whereas at double therapeutic doses, the two drugs showed highly significant increases in the total numbers of structural chromosomal aberrations compared with controls.The frequency of total chromosomal aberrations in mice's spermatocytes was increased at significant level p<0.01 for both drugs at therapeutic doses. At double therapeutic doses, pepon and postoplex increased the total chromosomal aberrations in spermatocyte cells at highly significant level p<0.001.In conclusion, the cytogenetic analysis of pepon and prostoplex revealed that the two drugs have adverse effect on somatic and germinal materials at therapeutic dose. Also, our results are considered as a caution for the treatment with these two drugs at double therapeutic doses, which have mutagenic effect on somatic and germinal materials.

Lack of alterations on meiotic chromosomes and morphological characteristics of male germ cells in mice exposed to a 60 Hz and 2.0 mT magnetic field.

The effect of in vivo exposure of mice to a 60 Hz sinusoidal magnetic field (MF) at 2.0 mT on male germ cells was studied. The cytological endpoints measured included meiotic chromosome aberrations in spermatocytes and sperm morphology. Three independent experiments were carried out: (a) animals exposed for 72 h, (b) 10 days/8 h daily, and (c) 72 h exposure to MF plus 5 mg/kg of Mitomycin-C. No statistically significant differences indicative of MF effects were observed between MF exposed and control animals. In addition, an opposite effect between MF exposure and Mitomycin-C treatment in terms of chromosomal aberrations and sperm morphology was observed.

Cytogenetic adaptive response with multiple small X-ray doses in mouse germ cells and its biological influence on the offspring of adapted males

Cytogenetic adaptive response of mouse germ cells was studied by exposing male mice to a sequence of 4 conditioning doses of 0.05 Gy each ( D1) administered at 10-day intervals and subsequently to a single challenging dose of 1.5 Gy ( D2). In concurrent experiments, male mice after treatment with D1 doses alone were mated to unirradiated females and the F1 males were given the D2 dose. Chromosomal aberrations in both spermatocytes and bone-marrow cells and UV-induced UDS in splenocytes of these mice were studied. Adapted mice (i.e., D1 + D2 exposures) responded with a significantly lower frequency of chromosomal aberrations than the non-adapted ( D2 exposure only) controls. The relative reduction in frequencies was, however, similar to that observed in earlier work with a single conditioning dose of 0.05 Gy. The frequencies of chromosomal aberrations in spermatocytes and bone-marrow cells as well as the levels of UV-induced UDS in splenocytes of the F1 males in the group D1 to fathers + D2 to F1 males were the same as those in F1 males which received only the D2 exposure

Induction of an adaptive response to dominant lethality and to chromosome damage of mouse germ cells by low dose radiation

In the present paper, dominant lethal mutations, chromosome aberrations in spermatocytes and reciprocal translocations in stem spermatogonia were analyzed after whole body exposure of mice to X-radiation. Results both from chromosome aberrations in spermatocytes and for reciprocal translocations in spermatogonia showed that pre-exposure to low doses up to 200 mGy could induce a significant dose-dependent reduction in adapted mice compared to the non-adapted mice; the lower the adaptive dose, the greater the reduction. For dominant lethal mutations, it was found that spermatogonia (both stem cells and differentiated cells) and spermatocytes adapted to 50 mGy X-rays could show an adaptive response, but spermatids and spermatozoa could not.

Dominant lethality in mice--a test for mutagenicity of influenza X-31 virus.

The induction of dominant lethal mutation in germ cells is the cause of embryonic death resulting in the reduction of litter size in the F1 progeny. Dominant lethal mutations were induced when male mice were infected with live A2 influenza virus. The chromosomal aberrations induced in the germ cells were shown to be responsible for the dominant lethality. Killed influenza virus was also potent in inducing chromosomal aberrations in spermatocytes of mice. In light of these observations, the UV-inactivated virus was tested for its potency in induction of dominant lethality in both female and male germ cells. The virus-inoculated females were mated with uninjected males and vice versa. Both the inactivated and live virus were found to induce dominant lethality in both female and male mice, indicating that not only the live virus but also the inactivated virus is capable of bringing about chromosomal damage resulting in dominant lethality.

Cytogenetic effects of microwave irradiation on male germ cells of the mouse.

Hybrid male mice were exposed to 2.45 GHz microwaves for 30 min/day, 6 days a week for two consecutive weeks at power densities of 1.0, 100 or 400 W m-2, with sham-exposed controls. Rectal temperatures before and after exposure were measured on days 1, 6 and 12. Measurements made on day 1 were treated with caution because of heterogeneity in rectal temperatures taken before exposure between the groups of mice given different treatments. On days 6 and 12, rectal temperatures rose by approximately 1 degree C in mice sham exposed, or exposed to 1 W m-2 or 100 W m-2. Only in the group of mice exposed to 400 W m-2 was the mean rise in rectal temperature during exposure (about 3 degrees C) significantly increased above the sham value. In groups killed 2-3 days after treatment (mainly meiotic exposure) frequencies of chromosome aberrations in spermatocytes showed no significant heterogeneity although the highest frequency of 1.5 per cent was at the highest (400 W m-2) power density. Another group killed 30 days after 100 W m-2 exposures (spermatogonial sampling) showed no significant increase over controls in chromosome aberration frequency. There was a small but significant increase in sperm count with increasing power density in mice killed 12-13 days after exposure, but a non-significant one in those exposed as spermatogonia (killed 41 days later). Thus effects were markedly less severe than those reported previously by Manikowska-Czerska et al. (1985) with a very similar radiation regime and were probably caused by the temperature enhancement.

Chromosome aberrations in spermatocytes and oocytes of mice irradiated prenatally

5 pregnant mice were exposed to a single dose of 150 R whole body γ-irradiation on the 12th day of gestation. The ocytes and spermatocytes, collected from the F1 progeny at ages 10–12 weeks, were examined for chromosome aberrations in metaphase I and compared with those of the progeny of non-irradiated controls. No differences were found in the type and frequency of aberrations between irradiated and controls nor between the sexes. It appears, therefore, that either primordial germ cells of both males and females are fairly resistant to radiation or an efficient selection or repair mechanism has eliminated the aberrant cells.

Chromosome aberrations in spermatocytes and oocytes of mice irradiated prenatally

5 pregnant mice were exposed to a single dose of 150 R whole body γ-irradiation on the 12th day of gestation. The ocytes and spermatocytes, collected from the F 1 progeny at ages 10–12 weeks, were examined for chromosome aberrations in metaphase I and compared with those of the progeny of non-irradiated controls. No differences were found in the type and frequency of aberrations between irradiated and controls nor between the sexes. It appears, therefore, that either primordial germ cells of both males and females are fairly resistant to radiation or an efficient selection or repair mechanism has eliminated the aberrant cells.