Radiation-induced chromosomal aberrations in the bone marrow of mice exposed to various doses of gamma radiation

The occurrence of chromosomal aberrations was studied at 1–14 days post-exposure in female BALB/c mice exposed to various doses of gamma radiation. The frequency of abnormal cells, chromatid and chromosome breaks, dicentrics, centric rings, acentric fragments and total aberrations increased with exposure dose, and it was highest at 7 Gy. A peak was recorded on day 1 post-exposure with a gradual decline thereafter. The chromosomal aberration yield reached a nadir on day 14 post-irradiation, without restoration to the control level. The best fit for the present data was by a linear-quadratic relationship between dose of radiation and the frequency of chromosomal aberrations.     

Niacin deficiency increases spontaneous and etoposide-induced chromosomal instability in rat bone marrow cells in vivo

Poly(ADP-ribose) polymerase (PARP) binds to DNA single and double strand breaks and uses NAD in the synthesis of poly(ADP-ribose) (pADPr). Niacin deficiency in rats decreases bone marrow NAD(+) and limits pADPr synthesis in response to DNA damage, while pharmacological supplementation with nicotinic acid (NA) increases bone marrow NAD(+) and pADPr. The purpose of this study was to determine if niacin status alters the extent of DNA damage and chromosomal instability before and after treatment with the chemotherapy drug etoposide (ETO). Genotoxicity was evaluated using the comet, micronucleus and sister chromatid exchange (SCE) assays. Male Long-Evans rats were fed niacin deficient (ND), or pair-fed (PF) niacin replete (30mg niacin/kg) or NA supplemented (4g niacin/kg) diets for 3 weeks. Rats were gavaged with ETO (1-25mg/kg) suspended in corn oil or an equal volume of vehicle (CON). Comet analysis demonstrated that ETO-induced DNA damage (mean tail moment (MTM) and proportion of cells with significant damage) was greater in bone marrow cells from ND rats, compared to PF or NA rats. Surprisingly, niacin deficiency alone caused 6.2- and 2.8-fold increases in spontaneous micronucleus formation and SCE frequency, respectively. As expected, ETO treatment increased the level of micronuclei (MN) and SCEs in all diet groups; however, the absolute increases were greater in ND bone marrow. These data show that niacin is required for the maintenance of chromosomal stability and may facilitate DNA repair in vivo, in a tissue that is sensitive to niacin depletion and impaired pADPr metabolism. Pharmacological intakes of niacin do not appear to be further protective compared to adequate intakes. Niacin supplementation may help to protect the bone marrow cells of cancer patients with compromised nutritional status from the side effects of genotoxic chemotherapy drugs.     

Clastogenicity of lanthanides: induction of chromosomal aberration in bone marrow cells of mice in vivo

Clastogenic properties of two lanthanide elements praseodymium (Pr) and neodymium (Nd) were evaluated by employing mouse in vivo chromosomal aberrations (CAs) assay. Praseodymium oxide (Pr₆O₁₁) and neodymium oxide (Nd₂O₃) administered intraperitoneally to Swiss albino mice in vivo induced significant increase in the frequency of CAs in bone marrow cells, when compared to negative control. The number of CAs/cell and percent aberrant cells increased with an increase in the concentration and period of treatment. The effect was maximum when the cells were analysed 12 h after treatment, as compared to 6 and 24 h. This is the first report on the clastogenicity of these elements in mouse in vivo.     

Suppression by bone marrow cells of the level of specific IgE antibodies in the blood of mice and decrease in the production of IGE by bone marrow cells

Changes in the level of the specific IgE-antibodies to ovalbumin under the influence of syngeneic cells of a bone marrow were studied. The IgE-response was induced by ovalbumin in mice (CBA X C57Bl/6)F1. The bone marrow cells suspensions (20-30 X 10(6) cells per mouse) from syngeneic donors was inoculated simultaneously with the immunization. It was found that bone marrow cells suppressed both the level of IgE-antibodies in experimental mice serum and the production of IgE by the bone marrow cells of the recipient. The ability to suppress IgE-response remained when erythrocytes, monocytes and T-lymphocytes were removed from inoculated suspensions. The bone marrow cells taken from the mice immunized with ovalbumin, at the stage of a decreasing IgE-response, provided more pronounced suppression, than bone marrow cells taken from intact animals.     

Correlation between the duration of radiation adaptive response in bone marrow cells of mice and the dose of gamma-irradiation in vivo

The dependence between the adaptive response and adaptive dose was studied on the basis of cytogenetic damage in polychromatic erythrocytes of bone marrow cells in mice after a low dose gamma-irradiation in vivo. The adaptive response to doses of 0.1 and 0.2 Gy was found to be retained for at least two months after irradiation. However, the adaptive dose of 0.4 Gy did not induce prolonged adaptive response.     

The induction of chromosomal aberrations by tetra antibiotic in bone marrow cells of rats in vivo

The aim of this study was to investigate the in vivo effects of Tetra (Tetralet) antibiotic on the chromosomal aberrations (CA) in bone marrow cells of rats (Rattus norvegicus var. albinos). Tetra antibiotic significantly increased the percentage of abnormal cells and the chromosomal aberrations per cells (CA/cell) in bone marrow cells of rats at concentrations of 100 and 200 mg/kg body weight for 12 and 24 hours treatment periods for each. In addition, the percentage of abnormal cells and the CA/cell increased dose-dependently for 12 hours treatment period; In contrast, mitotic index (MI) was decreased when compared with negative control and solvent controls for 12 hours treatment period. However, MI increased depend on Tetra antibiotic dose for 24 hour treatment period.     

The effect of glycerine on gamma-induced mutagenesis in Salmonella typhimurium cells

A study was made of the modifying effect of glycerol on the survival rate and gamma radiation-induced mutagenesis of Salmonella typhimurium cells TA98, TA100 and TA102. The DMF value, with respect to the survival rate, was 2.05-0.20. The dependence of the yield of gamma radiation-induced mutants on radiation dose was described by the curve with a maximum; the mutation frequency M(D) was well described by a gradual function M(D) = kDx. DMF values of the induced mutagenesis amounted to 2 for strains TA100 and TA102, and 1.5 for strain TA98.     

Fenvalerate-induced chromosome aberrations and sister chromatid exchanges in the bone marrow cells of mice in vivo

To investigate whether subjects with low-acid states are exposed to increased genetic risk with respect to controls, we evaluated mutagenicity and presence of clastogenic factors (CF) in the gastric juice of chronic atrophic gastritis and omeprazole-treated patients. Mutagenic gastric juice was found in 8/15 (53%) chronic atrophic gastritis patients, 8/11 (73%) omeprazole-treated patients, and 2/13 (15%) healthy control subjects. The mean mutagenicity ratio of omeprazole-treated patients (1.52+/-0.48/0.1 ml gastric juice) was significantly higher than those of either controls (1.07+/-0.15; P<0.01) or chronic atrophic gastritis patients (1.16+/-0.21; P<0.05). Only chronic atrophic gastritis patients showed an increased clastogenic index with respect to healthy controls (2.67+/-2.13 versus 0.38+/-0.51; P<0.001). These findings expand our knowledge of gastric disease risk factors, and indicate that there may well be a risk of mucosal DNA damage arising from the presence of mutagenic and CF in the gastric juice.     

Fenvalerate-induced chromosome aberrations and sister chromatid exchanges in the bone marrow cells of mice in vivo

Fenvalerate, a synthetic pyrethroid insecticide, is commonly used in agriculture and other domestic applications due to its high insecticidal activity and low mammalian-, avian- and phyto-toxicities. However, the genotoxic effect of fenvalerate is highly equivocal. In the present study the genotoxic effects of fenvalerate was evaluated using structural chromosome aberration (CA) and sister chromatid exchange (SCE) assays in mice. Out of the three doses (5, 10 and 20 mg/kg) tested, statistically significant increase in CA was found following intra peritoneal (i.p.) treatment of 20 mg/kg of fenvalerate for 24 h (P<0.01) and 48 h (P<0.05) only. Neither the acute doses of 5 and 10 mg/kg, nor the sub-acute dose (5×4 mg/kg) of fenvalerate could induce any significant effect. All the three acute doses induced significant increase in the frequency of SCEs (P<0.01) in the bone marrow cells, which showed a significant dose-response correlation (r=0.9541, P<0.05). With certain reservations to possible impurities, from the present findings technical grade fenvalerate may be considered as a weak clastogen and a potent inducer of SCEs in mice.     

Low doses of radiation increase the latency of spontaneous lymphomas and spinal osteosarcomas in cancer-prone,radiation-sensitive Trp53 heterozygous mice

Mice heterozygous for Trp53 are radiation-sensitive and cancer-prone, spontaneously developing a variety of cancer types. Osteosarcomas in the spine lead to paralysis, while lymphomas lead rapidly to death, distinct events that provide objective measures of latency. The effects of a single low-dose (10 or 100 mGy), low-dose-rate (0.5 mGy/min) (60)Co gamma irradiation on lymphoma or spinal osteosarcoma frequency and latency, defined as time of death or of onset of paralysis, respectively, were examined. Compared to spontaneous lymphomas or to spinal osteosarcomas leading to paralysis in unexposed mice, an exposure of 7-8-week-old Trp53(+/-) mice to 10 or 100 mGy had no significant effect on tumor frequency, indicating no effect on tumor initiation. All tumors are therefore assumed to be of spontaneous origin. However, a 10-mGy exposure reduced the risk of both lymphomas and spinal osteosarcomas by significantly increasing tumor latency, indicating that the main in vivo effect of a low-dose exposure is a reduction in the rate at which spontaneously initiated cells progress to malignancy. The effect of this adaptive response persisted for the entire life span of all the animals that developed these tumors. Exposure to 100 mGy delayed lymphoma latency longer than the 10-mGy exposure. However, the 100-mGy dose increased spinal osteosarcoma risk by decreasing overall latency compared to unexposed control mice. That result suggested that this higher dose was in a transition zone between reduced and increased risk, but that the dose at which the transition occurs varies with the tumor type.     

Clastogenicity effect of ruthenium red in vivo, in bone marrow cells in mice

The ability of ruthenium red to induce chromosome aberrations in vivo in mammalian somatic cells has been evaluated by the micronucleus test on mouse bone marrow cells. Our results show that this compound, when administered i.p. at a sublethal level, can be considered as a weak clastogen.     

Ultrastructural study of spontaneous bone marrow rosette-forming cells

Mouse bone marrow contains spontaneous rosette-forming cells (RFC) which include more than 70% T-cell precursors, as assessed by their transformation into theta-positive cells after incubation with thymic hormone. Such spontaneous RFC, examined in C57B1/6 mouse bone marrow by electron and scanning electron microscopy, have consistently been shown to be small, inactive mouse lymphocytes when macrophages have been eliminated by cell preincubation. These data suggest that thymic hormone target cells include small quiescent lymphocytes.     

Hematopoietic precursor cells in radiation chimeras restored by bone marrow from thymectomized mice]

Radioprotective capacity of bone marrow CFUs of adult thymectomized mice was studied. Lethally irradiated mice were inoculated with bone marrow of mice thymectomized 8-11 months before. The colony forming capacity and proliferative rate of CFUs were studied 1-7.5 months after obtaining the radiation chimeras. It has been shown that proliferative capacity of bone marrow of adult thymectomized mice was reduced in comparison with that of normal animals. It is related to the decrease (4-fold) of the proliferative rate of bone marrow of thymectomized mice which was inoculated into lethally irradiated recipients 1 month before. We also found that the content of CFUs in bone of those chimeras was reduced later--after 7.5 months. In this period (1-7.5 months) the cellularity of bone marrow did not change.     

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.