Cytogenetic effects of malathion insecticide on somatic and germ cells of mice

Male mice dermally exposed to single or multiple treatment (5 days/2 weeks) showed that the ability of malathion to induce chromosome aberrations in somatic (bone marrow) and germ cells (primary spermatocytes) was related to the type of treatment and dose used. Statistically significant increases of chromosome aberrations in bone marrow cells occurred after single treatment (500 and 2000 mg/kg body wt) when chromatid gaps were included and after multiple treatment (250 and 500 mg/kg) when they were excluded. No dose-response relationships were observed for either treatment. In germ cells, malathion induced a significant increase of univalents in both types of treatment but structural chromosome aberrations were induced only by multiple treatment. Malathion induced a significant decrease of the mitotic indices in the bone marrow.     

A comparative study on the genotoxic effect of pyrimethamine in bone marrow and spermatogonial mice cells

Pyrimethamine is an antimalarial agent widely used in clinical therapy. We aimed to compare its mutagenic potential in mammalian spermatogonial and bone marrow cells. For studying chromosomal aberrations mice were treated acutely (single treatment) with 4 dose levels of pyrimethamine (5, 10, 20 and 40 mg/kg). Pyrimethamine was found to produce a significant increase in structural chromosomal aberrations after acute treatment in bone marrow cells of mice (p < 0.001). It also induced chromosome abnormalities in spermatogonial cells (p < 0.05) at the highest dose.     

Suppressing effects of vanillin,cinnamaldehyde, and anisaldehyde on chromosome aberrations induced by X-rays in mice

X-ray-induced chromosome aberrations were suppressed when vanillin, cinnamaldehyde, or p-anisaldehyde was given orally to mice after X-ray irradiation. Chromosome aberrations were monitored by the occurrence of polychromatic erythrocytes with micronuclei in bone marrow cells. The frequency of micronuclei was depressed about 55–60% without toxicity of the test compounds to the bone marrow.     

Spontaneous and induced chromosome aberrations in the bone marrow cells of different strains of mice during aging

Sensitivity of bone marrow cell chromosomes to alkylating agent thiophosphamide and to gamma-irradiation has been studied in the course of ageing in 101/H, A/He, CBA, BALB/c and C57BL/6 mice. The effects of both the kinds of mutagenic treatment and of the genotype of the animals on the age-dependent changes in sensitivity of bone marrow cell chromosomes were found. Following gamma-irradiation under our experimental conditions, no variation in the output of chromosomal aberrations was observed between the strains studied. Following thiophosphamide treatment, aged mice of strains 101/H, A/He and CBA showed an increased chromosome instability as compared to young ones. In C57BL/6 mice the level of induced chromosome aberrations was found to be age-independent. Following thiophosphamide treatment, cells with multiple chromosome lesions were found in the bone marrow. The higher instability of aged animals in some strains was mainly due to a sharp increase in the number of such cells. In the intact mice of all the strains studied no age-dependent increase in the number of cells showing structural chromosome aberrations was observed, while accumulation of aneuploid cells varied with genotype.     

Long-term effects of low-level 239Pu contamination on murine bone-marrow stem cells and their progeny

The effects of long-term internal contamination with 13.3 kBq kg-1 239Pu injected intravenously were studied in 10-week-old ICR (SPF) female mice. Radiosensitivity of spleen colony-forming units (CFU-S) and 125IUdR incorporating into proliferating cells of vertebral bone marrow and spleens were determined in plutonium-treated and control animals one year after nuclide injection. The CFU-S in 239Pu-treated mice were more sensitive to X-rays (D0 = 0.52 +/- 0.01 Gy) than in controls (D0 = 0.84 +/- 0.02 Gy). 125IUdR incorporation into bone marrow and spleen cells was reduced after plutonium contamination. At one year following plutonium injection, the occurrence of chromosome aberrations was evaluated in metaphase figures of femoral bone marrow cells. The frequency of aberrations increased early after plutonium treatment, at later intervals it tended to decrease but not below the control level. While the relative numbers of vertebral marrow CFU-S decreased significantly, but only to 86 per cent of normal, cellularity of vertebral bone marrow, peripheral blood counts and survival of 239Pu-treated mice did not differ from the control data.     

Cytogenetic effect of mitomycin C and cytosine arabinoside on mice of different genotypes]

Cytogenetic effect of mitomycin C (MC) and cytosine arabinoside (CA) on bone marrow cells of male mice of the strains 101/HY, C57BL/6Y C,3H/SnY and of the (C3HX101) F1 hybrids was studied. The frequencies of cells with chromosome aberrations after the treatment with MC at a 5 mg/kg dose were 54,4%; 41,8%; 40,4% and 26,8% in 101H, B6, C3H/Sn mice and in the F1 hybrids (C3HX101) respectively. The frequencies of cells with chromosome aberrations after the treatment with CA at a 500 mg/kg dose were 25,2%; 17,8%; 10,8% and the 101/H, B6, C3H/Sn mice and in the F1 hybrids (C3HX101) respectively. Both mutagens induced the greatest number of chromosome aberrations in the 101/H strain and the smallest number in the F1 hybrid (C3HX101). A positive correlation was established between the levels of induced and spontaneous chromosome lesions.     

Possible mutagenic action of a tularemia vaccine

No increase in the number of chromosome aberrations in the bone marrow cells of the Wistar rats was observed on the 1st, 2nd, 7th and 15th days after epidermal and intradermal immunization by tularemic live vaccine. Subcutaneous injection of great quantities of tularemic microbic cells which were not used in practice increased the number of cells with chromosome aberrations only on the second day.     

A correlative study on the genetic damage induced by chemical mutagens in bone marrow and spermatogonia of mice : I. CNU-ethanol

Cytogenetic damage induced by a wide range of concentrations of CNU-ethanol in mice was evaluated by determining the frequencies of (a) micronuclei nuclei in polychromatic erythrocytes of the bone marrow, (b) chromatid aberrations in bone marrow, (c) chromatid aberrations in spermatogonia, and (d) reciprocal translocations induced in spermatogonia and scored in spermatocytes.For CNU-ethanol the following order of sensitivity was found between the tests performed: micronuclei > aberrations in bone marrow > aberrations in spermatogonia > translocations in spermatocytes.Correlation coefficients were calculated for the first three parameters. Positive correlations existed (a) between micronuclei in polychromatic erythrocytes and chromatid aberrations in bone marrow on the first day after treatment, and (b) between chromatid aberrations in bone marrow and spermatogonia at the first day after treatment.Three reciprocal translocations were induced in spermatogonia and recorded in primary spermatocytes; all were of a rare type, namely between an X chromosome and an autosome.     

Relation of the frequency of chromosome aberrations in mouse bone marrow cells to the concentration (dose) of benzene administered by various routes

Experiments on mice were made to study the rate of bone marrow cells with chromosome aberrations after continuous inhalation of benzene for 7 days at the concentrations 13.9, 36.8 and 73.7 mg/m3 and after a 10-fold intragastric administration of benzene at the doses 5,20 and 80 mg/kg, the interval between administrations being 24 hours. The rate of cells with chromosome aberrations increased as the benzene level was raised (upon both administration routes) and was satisfactorily depicted by linear equations. The doses 36.8 and 20 mg/kg appeared the least effective.     

The protective effect of beta-carotene on genotoxicity induced by cyclophosphamide.

The influence of beta-carotene on the clastogenicity of the indirect-acting mutagen cyclophosphamide (CPA) was investigated in mice, in vivo, for the induction of chromosome aberrations in bone marrow cells (BM). beta-Carotene (0.5, 1.0, 2.0, 5.0, 10, 25, 50, 100 and 200 mg/kg) was administered by gavage for 5 consecutive days. 4 h after the last treatment with beta-carotene, the mice were injected intraperitoneally with CPA, and the BM cells were fixed after 16, 24 and 32 h for the evaluation of the frequency of chromosome aberrations. The results showed that beta-carotene was effective in reducing chromosomal damage induced by CPA with the increase of its concentration up to a level after which this effect was not observed. This anticlastogenicity was better detected when the cells were fixed at 32 h, although a tendency in reducing the CPA clastogenicity was already observed at 16 and 24 h. Our results suggest that beta-carotene provides significant protection against the genotoxicity of CPA, although no dose-effect relationship on the frequencies of cells with chromosomal aberrations was observed.     

DNA-repair kinetics and the sensitivity of cells to X-ray-induced chromosome aberrations: a mouse myeloid leukemia cell line and normal mouse bone marrow cells

The frequency of X-ray-induced chromosome aberrations in G1 ML-1 mouse myeloid leukemia cells and normal mouse bone marrow cells increased with post-irradiation incubation with the DNA-repair resynthesis inhibitor 1-beta-D-arabinofuranosylcytosine (araC), but the frequency of aberrations in the leukemic cells increased with quite a different time response compared to the normal cells. Irradiated normal mouse bone marrow cells had a rapid increase in the frequency of chromosome exchanges and deletions with increasing araC incubation time, for example, an increase was observed with 0.5 h araC incubation. In contrast, the ML-1 cells did not have a significant increase in aberrations until 1-2 h post-irradiation incubation with araC. These results suggest that the ML-1 cells, per unit time, initially undergo less repair of the X-ray-induced DNA damage that can be converted into chromosome aberrations. We previously showed that the ML-1 cells have a higher frequency of X-ray-induced chromosome aberrations compared to normal cells and the results presented here indicate that a slower rate of repair resynthesis is contributing to the increased sensitivity of the ML-1 cells.     

Anticlastogenic effects of a polyvitamin product, 'Pharmavit', on gamma-ray induction of somatic and germ cell chromosome aberrations in the mouse.

The polyvitamin product 'Pharmavit' (Pv), comprising vitamins A, D2, B1, B2, B6, C, E, nicotinamide, and calcium pantothene, was tested for anticlastogenic properties against gamma-rays in mice. Pretreatment with Pv consisted of daily administration by gavage for 30 days at dose levels corresponding to clinical recommendations for an adult human, as recalculated in terms of mg/kg. Findings indicated a reduction of chromosome aberrations in bone marrow cells from mice exposed to 3.0 Gy 137Cs gamma-rays; the reduction concerned predominantly fragments of the chromatid type. Furthermore, a reduction factor of 1.6 was obtained for the frequency of reciprocal translocations induced by spermatogonial irradiation in mice exposed to 4.0 Gy gamma-rays. Pretreatment with vitamin C alone, at the dose present in Pv, proved nearly ineffective in protecting from chromosome aberrations in bone marrow cells. Pharmavit is believed to be a promising agent for application to human populations exposed to the carcinogenic and genetic hazards of ionizing radiation.     

Acceleration of chromosome aberrations in senescence-accelerated strains of mice

Age-related changes in the frequency of chromosome aberrations were examined using bone marrow cells of senescence-accelerated strains of mice (SAM). An accelerated senescence-prone strain, SAM-P/1, showed a striking increase in the frequency of chromosome aberrations, from age 3 to 8 months, whereas an accelerated senescence-resistant strain, SAM-R/1, at the same ages showed only a slight increase. Both these strains were derived from the same ancestral strain (AKR/J). The rate of increase of chromosome aberration frequency paralleled the advancement of senescence in both strains. These observations suggest that there are genetic factors which closely relate to chromosomal instability and acceleration of the senescence processes.     

Clastogenic effects of cis-diamminedichloroplatinum. I. Induction of chromosomal aberrations in somatic and germinal cells of mice

The clastogenicity of cisplatin, cis-diamminedichloroplatinum(II), an extensively used antitumor drug, has been studied employing (101/E1 X C3H/E1)F1 mice, aged 12-14 weeks. Chromosomal aberrations were assessed in mitotic divisions of bone marrow cells and differentiating spermatogonia. The drug was tested at 3 doses, 0.5, 1.0 and 2.5 mg/kg and 1.0, 2.5 and 5.0 mg/kg, respectively, for bone marrow and spermatogonia. Cisplatin had a clastogenic effect which was dose-dependent in both cell types. The frequencies of aberrant cells increased non-linearly in bone marrow and the dose-response relationship could be best described by a linear-quadratic equation. At the highest dose the affected cells carried multiple aberrations. An average of 2.7 aberrations per aberrant cell was observed 12 h after treatment of the mice with 2.5 mg/kg of cisplatin. In differentiating spermatogonia the dose response for aberrant cells could be described by a linear equation. The damage to the individual affected cell was less dramatic than in bone marrow, averaging 1.4 aberrations per damaged cell at the highest dose tested. Gaps were excluded from these considerations but they generally also showed a dose-related increase. A quantitative comparison of the clastogenic response to cisplatin was based on the dose-response relationships using 2 criteria, the doubling dose and the dose of unit increase (DUI). For both comparisons the general conclusion was that bone marrow cells were twice as sensitive as differentiating spermatogonia to the clastogenic action of cisplatin.     

Mentha piperita (Linn.) leaf extract provides protection against radiation induced chromosomal damage in bone marrow of mice

Oral administration of M. piperita (1 g/kg body weight/day) before exposure to gamma radiation was found to be effective in protecting against the chromosomal damage in bone marrow of Swiss albino mice. Animals exposed to 8 Gy gamma radiation showed chromosomal aberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges and acentric fragments. There was a significant increase in the frequency of aberrant cells at 6 hr after irradiation. Maximum aberrant cells were observed at 12 hr post-irradiation autopsy time. Further, the frequency of aberrant cells showed decline at late post-irradiation autopsy time. However, in the animals pretreated with Mentha extract, there was a significant decrease in the frequency of aberrant cells as compared to the irradiated control. Also significant increase in percentage of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges, acentric fragments, total aberrations and aberrations/damaged cell was observed at 12 hr post-irradiation autopsy time in control animals, whereas Mentha pretreated irradiated animals showed a significant decrease in percentage of such aberrations. A significant decrease in GSH content and increase in LPO level was observed in control animals, whereas Mentha pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPO level but the values remained below the normal. The radioprotective effect of Mentha was also demonstrated by determining the LD(50/30) values (DRF = 1.78). The results from the present study suggest that Mentha pretreatment provides protection against radiation induced chromosomal damage in bone marrow of Swiss albino mice.     

Chromosome aberrations do not persist in the lymphocytes or bone marrow cells of mice irradiated in utero or soon after birth

Mice were exposed at various ages to 1 Gy or 2 Gy of X rays, and translocation frequencies in peripheral blood T cells, spleen cells, and bone marrow cells were determined with FISH painting of chromosomes 1 and 3 when the animals were 20 weeks old. It was found that the mean translocation frequencies were very low (< or =0.8%) in mice exposed in the fetal or early postnatal stages. However, with the increase in animal age at the time of irradiation, the frequency observed at 20 weeks old became progressively higher then reached a plateau (about 5%) when mice were irradiated when > or =6 weeks old. A major role of p53 (Trp53)-dependent apoptosis for elimination of aberrant cells was not suggested because irradiated fetuses, regardless of the p53 gene status, showed low translocation frequencies (1.8% in p53(-/-) mice and 1.4% in p53(+/-) mice) compared to the frequency in the p53(-/-) mother (7.4%). In contrast, various types of aberrations were seen in spleen and liver cells when neonates were examined shortly after irradiation, similar to what was observed in bone marrow cells after irradiation in adults. We interpreted the results as indicating that fetal cells are generally sensitive to induction of chromosome aberrations but that the aberrant cells do not persist because fetal stem cells tend to be free of aberrations and their progeny replace the pre-existing cell populations during the postnatal growth of the animals.     

Genetic effects of hyperbaric oxygen therapy

Patients with several diseases have been examined for detection of chromosome aberrations in peripheral blood cells after 10 sessions of hyperbaric oxygen (HBO) at 0.15-0.20 MPa for 40 min. The present study reveals that HBO increases the level of chromosome aberrations, and that individual reactions to HBO differ. Pure erythrocytes treated with high-pressure oxygen (HBO) at 0.7 MPa for 1 h are clastogenic for intact syngeneic lymphocytes. The effect of HBO (0.3 MPa, 5 sessions of 1 h daily) on induction of chromosome aberrations in somatic cells and germinal tissues of rat males has been studied. Induction of aberrations in bone marrow cells after HBO was seen for 3 months. In lymphocytes of patients, it was seen for 9 months. Chromosome rearrangements at the first meiotic division were detected only 90 days after exposure. HBO affects neither the functional nor the morphological condition of gonads and does not induce dominant lethals. It is proposed that a high quantity of chromosome breaks in cells of somatic tissues is an adaptive reaction of organisms to HBO.     

Action of mitomycin C on mouse spermatogonia

The induction of chromosome aberrations in mouse spermatogonia and bone marrow cells by treatment with Mitomycin (MC) was tested. The following dosages were used: 3.5; 1.75; 0.35; and 0.035 mg/kg body weight. Chromatid interchanges and terminal deletions were induced in both tissues. Regarding the chromosome damage, spermatogonia seemed to be more sensitive to the test substance than bone marrow cells.The aberrations observed were considered to represent the cause of dominant lethals induced in spermatocytes after treatment with MC by others. The squash technique adapted for examination of mitoses of mouse spermatogonia proved to be a useful tool in testing potential chemical mutagens.     

Radioprotective effects of Dragon's blood and its extract against gamma irradiation in mouse bone marrow cells

PurposeThe radioprotective effects of Dragon's blood (DB) and its extracts (DBE) were investigated using the chromosomal aberrant test, micronucleus and oxidative stress assay for anti-clastogenic and anti-oxidative activity.Materials and methodsAdult BALB/C mice were exposed to the whole body irradiation with 4 Gy ⁶⁰Co γ-rays. DB and DBE were administered orally once a day from 5 days prior to irradiation treatment to 1 day after irradiation. The mice were sacrificed on 24 h after irradiation. The cells of bone marrow were measured by counting different types of chromosomal aberrations and the frequency of micronuclei. Oxidative stress response was carried out by analysis of serum from blood.ResultsDB and DBE significantly decreased the number of bone marrow cells with chromosome aberrations after irradiation with respect to irradiated alone group. The administration of DB and DBE also significantly reduced the frequencies of micronucleated polychromatic erythrocytes (MPCE) and micronucleated normochromatic erythrocytes (MNCE). In addition, DB and DBE markedly increased the activity of antioxidant enzymes and the level of antioxidant molecular. Malondialdehyde (MDA) and nitric oxide (NO) levels in serum were significantly reduced by DB and DBE treatment.ConclusionsOur data suggested that DB and DBE have potential radioprotective properties in mouse bone marrow after ⁶⁰Co γ-ray exposure, which support their candidature as a potential radioprotective agent.     

Acute cytogenetic effects of potassium bromate on rat bone marrow cells in vivo

The acute cytogenetic effects of potassium bromate (KBrO3) on rat bone marrow cells in vivo were studied. The incidence of chromosome aberrations in bone marrow cells increased rapidly, reaching a maximum level 12 h after intraperitoneal injection and decreased within 24 h. Dose-response relationships were obtained for both intraperitoneal and oral administrations.