In vivo sister chromatid exchange induced by 1,2-dichloroethane on bone marrow cells of mice (original) (raw)
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Toxicology and Applied Pharmacology, 1986
Administration of cyclophosphamide (5, 10, 20 and 25 mg/kg body weight) to male CD-I mice 2 hr after subcutaneous implantation of a 5-bromo-2'-deoxyuridine (BrdUrd) pellet (55 mg) resulted in a dose-dependent increase in sister chromatid exchanges (SCE) in bone marrow cells. Treatment with cyclophosphamide (15 mg/kg body weight) at the time of BrdUrd implantation and 2, 6.5. and 13 hr post-BrdUrd implantation resulted in the induction of approximately 19 SCE/cell indicating that the bone marrow SCE response was independent of the time of administration. Treatment with cyclophosphamide (15 mg/kg body weight) at 26, 19, 13, and 6 hr prior to BrdUrd implantation resulted in baseline SCE (3.3 SCE/cell) at 26 hr with an increasing number of SCE/cell with decreasing time prior to BrdUrd implantation. These results compare favorably with those obtained by Kram et al [ 19811 with mitomycin C (MMC) using a similar protocol. The time-dependent induction of SCE is qualitatively similar for CP and MMC, both of which are bifunctional alkylating agents metabolically activated by oxidation and reduction, respectively, and suggests that these two compounds may induce SCE by a similar mechanism.
Sister chromatid exchange induction near the baseline with low doses of the alkylating agent CCNU
Environmental and molecular mutagenesis, 1988
Sister chromatid exchange (SCE) and cell-cycle kinetics were examined at near-baseline levels in human peripheral lymphocytes exposed to low doses of the potent SCE inducer 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), in vitro. A preliminary SCE dose-response curve was determined with a broad range of doses of CCNU using a single donor. SCE induction was approximately linear over the entire dose range from 5 to 200 microM CCNU. Cell cycle kinetics were retarded in a dose-dependent manner. A second dose-response curve from the same donor was constructed using several doses of CCNU between 0.5 and 10 microM to evaluate linearity and uniformity of SCE response near baseline levels. SCE induction was approximately linear between 1.0 and 10.0 microM CCNU. Finally, SCE and cell-cycle kinetics were examined in 12 donors at doses of 1.0, 5.0, and 10.0 microM CCNU to evaluate the reproducibility of near-baseline SCE induction over a range of subjects. Cell-cycle kinetics were retarde...
Environmental mutagenesis, 1983
Administration of cyclophosphamide (5, 10, 20 and 25 mg/kg body weight) to male CD-1 mice 2 hr after subcutaneous implantation of a 5-bromo-2'-deoxyuridine (BrdUrd) pellet (55 mg) resulted in a dose-dependent increase in sister chromatid exchanges (SCE) in bone marrow cells. Treatment with cyclophosphamide (15 mg/kg body weight) at the time of BrdUrd implantation and 2, 6.5, and 13 hr post-BrdUrd implantation resulted in the induction of approximately 19 SCE/cell indicating that the bone marrow SCE response was independent of the time of administration. Treatment with cyclophosphamide (15 mg/kg body weight) at 26, 19, 13, and 6 hr prior to BrdUrd implantation resulted in baseline SCE (3.3 SCE/cell) at 26 hr with an increasing number of SCE/cell with decreasing time prior to BrdUrd implantation. These results compare favorably with those obtained by Kram et al [1981] with mitomycin C (MMC) using a similar protocol. The time-dependent induction of SCE is qualitatively similar for ...
Environmental Health Perspectives, 1987
The purpose of this study was to assess sister chromatid exchange (SCE) levels and cell cycle kinetics in various murine tissues following MIC exposure. Following exposure of mice to MIC, these parameters were measured in bone marrow and alveolar macrophages labeled with BrdUrd in vivo and in peripheral blood and spleen lymphocytes cultured in the presence of BrdUrd in vitro. Target concentrations of MIC were 2, 15, and 30 ppm (3 hr). Neither elevated SCE frequencies nor inhibition of cell cycling were evident in lipopolysaccharide (LPS)or concanavalin A (ConA)-stimulated spleen lymphocytes, or in LPS-stimulated peripheral blood lymphocyte (PBL) cultures from mice exposed for 3 hr to MIC concentrations as high as 30.5 ppm. Inhibition of cell cycling and poor culture success rates were apparent in ConA-stimulated PBLs following MIC exposures as low as 2.3 ± 0.4 ppm for 3 hr. At the lowest MIC dose employed, the cycling characteristics of bone marrow and alveolar macrophages were not altered, and SCE frequencies were at control levels. However, severe cell cycle inhibition was observed in these tissues at MIC concentrations of 15 ppm or greater. A marker of cytotoxicity at this dose was a high frequency (approximately 33-90%) of occurrence of first division cells containing a latereplicating Y chromosome. Despite its apparent cellular toxicity, MIC is not genotoxic as measured by SCE analysis in the tissues examined in this study.
Mutagenesis, 2003
The public health effects of pesticides cannot be denied. However, the undesired effects of chemical pesticides have been recognized as a serious public health concern during the past decades. The present study describes the genotoxic effects of two pesticides, namely cypermethrin and carbosulfan, in a murine test system in vivo. The test parameter used was analysis of sister chromatid exchanges (SCE) in bone marrow cells. Both cypermethrin (5, 10 and 20 mg/kg) and carbosulfan (1.25, 2.5 and 5 mg/kg) induced significant increases in the frequency of SCEs (P < 0.001). However, no significant dose-response correlation could be found for either of the pesticides. Carbosulfan induced a cell cycle delay, as evidenced by an increase in average generation time accompanied by accumulation of cells in the first division cycle, but cypermethrin did not induce any such response. The present study indicates that carbosulfan has a higher potential to cause genetic alterations than cypermethrin in mice and may also pose a mutagenic risk to human beings.
Cytogenetic Effects of 1,1-Dichloroethane in Mice Bone Marrow Cells
International Journal of Environmental Research and Public Health, 2005
The major concern for the halogenated compounds is their widespread distribution, in addition to occupational exposures. Several chlorinated alkanes and alkenes were found to induce toxic effects. In this study, we investigated the genotoxic potential of 1,1-dichloroethane in the bone marrow cells obtained from Swiss-Webster mice, using chromosomal aberrations (CA), mitotic index (MI), and micronuclei (MN) formation as toxicological endpoints. Five groups of three male mice each, weighing an average of 24 + 2 g, were injected intraperitoneally, once with doses of 100, 200, 300, 400, 500 mg/kg body weight (BW) of 1,1-dichloroethane dissolved in ethanol. A control group was also made of three animals injected with ethanol (1%) without the chemical. All animals were sacrificed 24 hours after the treatment. Chromosome and micronuclei preparations were obtained from bone marrow cells following standard protocols. Chromatid and chromosome aberrations were investigated in 100 metaphase cells per animal and percent micronuclei frequencies were investigated in 1,000 metaphase cells per animal. 1,1-dichloroethane exposures significantly increased the number of chromosomal aberrations and the frequency of micronucleated cells in the bone marrow cells of Swiss-Webster mice.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 1997
The study was designed to determine the antigenotoxic potential of chlorophyllin Chl , against the frequency of Ž. w x Ž w x. sister-chromatid exchanges SCE produced by benzo a pyrene B a P in vivo. We used the mouse bone marrow test w x system to measure the effect of a single injection of the compounds: 40 mgrkg of B a P, and 1 h later, 1.0, 2.0, 4.0 and 8.0 Ž mgrkg of Chl. As controls we included both chemicals using the dosages mentioned above as well as mineral oil 0.25. Ž. mgrkg. The results indicated the following: 1 Chl per se was not genotoxic, showing SCE values in the range of the Ž. w x Ž. control level; 2 B a P increased the rate of SCEs three times in relation to the basal level; 3 the SCE level produced with w x B a P was diminished by all 4 doses of Chl, but better results were obtained with 2-4 mgrkg, a range which induced Ž. Inhibition Indices of 80.9% and 77.5% respectively; 4 the Average Generation Time Index was not modified by the Ž. compounds used in the experiment; and 5 the Mitotic Index also showed no significant modification induced by the chemicals, with respect to the control value.
Cancer research, 1984
Cyclophosphamide (CPA) is known to exert greater toxic effects of B- than on T-lymphocytes in vivo. Both in vitro and in vivo CPA treatments were used to assess the possible cytogenetic basis for these observations. First, male C57BL/6 mouse lymphocytes were stimulated to divide in vitro with either phytohemagglutinin (T-cell mitogen) or lipopolysaccharide (B-cell mitogen), and were then treated with CPA (0.05 to 1.0 mM) and 5-bromo-2'-deoxyuridine (2 microM) at 24 hr. Cultures were harvested at 60 hr following a 4-hr treatment with demecolcine (1.35 microM). CPA caused concentration-related increases in sister chromatid exchange (SCE) up to 3 times control frequencies; the resulting SCE induction curves for B- and T-cells were sigmoidal and equivalent. Second, mice were given a single i.p. injection of CPA (0.5, 1.0, or 5.0 mg/kg). Blood was removed 24 hr later and cultured without additional CPA, as described above. Dose-related increases in SCE frequencies were seen for both ...
Cell Biology and Toxicology, 1987
Frequencies of sister chromatid exchanges and chromosomal aberrations were examined in peripheral lymphocytes of Rhesus monkeys which had been fed a diet containing 25 parts per trillion 2,3, 7,8-tetrachlorodibenzo-p-dioxin for a period of 4 years. When compared to non-exposed control animals, no significant differences were noted for either of these cytogenetic endpoints. In addition, there was not a significant difference in sister chromatid exchange response to a challenge dose of mitomycin C in cells from 2,3, 7,8-tetrachlorodibenzo-p-dioxin exposed animals compared to controls. Our results confirm the lack of genotoxic effects associated with 2, 3, 7,8-tetrachlorodibenzo-p-dioxin exposure.