Genotoxic effects of dithane M-45 on the bone marrow cells of mice in vivo

Genotoxic effects of dithane M-45 were studied on the bone marrow cells of male albino mice (Lacca strain) in vivo. Different doses (30 mg, 40 mg and 300 mg/kg b.wt) of dithane M-45 were injected intraperitoneally and their effects were investigated after time intervals of 1, 2, 5 and 10 days. The chromosomal aberrations observed in the bone marrow cells of male mice after treatment with dithane M-45 were fragments, rings, dicentric chromosomes, terminal chromatid deletions, chromatid gaps and breaks. In addition to these chromosomal aberrations, physiological effects such as uneven stretching of chromatin material, end-to-end chromosomal associations, exchange configurations, clumping, stickiness and centromeric associations were also observed.     

Cytogenetic analysis of bone marrow cells and spermatogonia of male mice after in vivo treatment with arsenic

Summary Male Swiss Albino mice were injected i.p. with an As₂O₃ solution (0; 4; 8 and 12 mg As/kg) and sacrificed 12, 24, 36 and 48 h after injection. Neither chromatid nor chromosome aberrations were observed in bone marrow cells and spermatogonia.Acknowledgments. We thank Mr L. De Langhe for skillfull technical help. We acknowledge this work was supported by a grant of the Ministery of Public Health.     

Chromosome aberrations in mice by the antifungal antibiotic,nystatin

Summary Nystatin, a fungicide of current medical use, was tasted in mice for its effect on chromosomes of bone marrow cells. A significant increase of aberrations, mostly of chromatid type, was observed over a period of from 15 min to 15 days following the application of the drug. Our data indicate a non-random distribution of the breaks.     

Increases in frequency of sister chromatid exchange following tumor grafts in different immunocompetent hosts]

Measurement of sister chromatid exchanges (SCEs) frequency of inbred Rat or nu/nu Mice bone marrow cells, following tumour grafts, have been developed. Increase of SCEs was observed in hosts which present or not metases and with reduced survival rates after malignant tumour grafts. These results suggest a remote control of tumoral tissue by a diffused matter effect.     

Induction of chromosomal aberrations by the anthracycline antitumor antibiotics N,N-dimethyldaunomycin and aclacinomycin A

Summary The clastogenic effect of the anthracycline antitumor antibiotics, N,N-dimethyldaunomycin and aclacinomycin A, was studied in a murine hemopoietic cell line (Friend leukemia cells). A dose-dependent increase in chromatid lesions, i.e., achromatic lesions, chromatid breaks, chromatid deletions and triradial or quadriradial chromosomal exchange figures, was found. It appears that the clastogenicity of N,N-dimethyldaunomycin and aclacinomycin A is lower than that of the classic anthracycline, daunomycin, which is also a potent mutagen and carcinogen. The data demonstrate that the capacity of chemicals to induce point mutations and chromosomal aberrations may not necessarily be correlated: aclacinomycin A is devoid of mutagenic activity in bacterial (Salmonella typh.) and mammalian cell (HGPRT) mutagenesis assays, and is non-carcinogenic in rats. Nevertheless, it was now found to possess clastogenic activity.     

Induction of chromosomal aberrations by the anthracycline antitumor antibiotics N,N-dimethyldaunomycin and aclacinomycin A

The clastogenic effect of the anthracycline antitumor antibiotics, N,N-dimethyldaunomycin and aclarcinomycin A, was studied in a murine hemopoietic cell line (Friend leukemia cells). A dose-dependent increase in chromatid lesions, i.e., achromatic lesions, chromatid breaks, chromatid deletions and triradial or quandriradial chromosomal exchange fiqures, was found. It appears that the clastogenicity of N,N-dimethyldaunomycin and aclacinomycin A is lower than that of the classic anthracycline, daunomycin, which is also a potent mutagen and carcinogen. The data demonstrate that the capacity of chemicals to induce point mutations and chromosomal aberrations may not necessarily be correlated: aclacinomycin A is devoid of mutagenic activity in bacterial (Salmonella typh.) and mammalian cell (HGPRT) mutagenesis assays, and is non-carcinogenic in rats. Nevertheless, it was now found to possess clastogenic activity.     

Effect of azimexon (BM 12.531) on mouse granulocyte-macrophage and monocyte-macrophage progenitor cells

Summary Treatment of mice with 25 mg/kg azimexon (BM 12.531) resulted in an increase in granulocyte-macrophage colony-forming cells (GM-CFC) in spleen and bone marrow after a transient depression in the cell populations. Bone marrow monocyte-macrophage colony-forming cells (MM-CFC) increased at 7 days after treatment, and splenic MM-CFC were least affected by azimexon treatment. The increase in granulocytic and monocytic colony-forming cells may play a role in the previously reported protection by azimexon against radiation and drug-induced toxicity.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under Research Work Unit MJ 00026.     

X-ray induction of chromosome and chromatid aberrations in the same cells after treatment with hydroxyurea

Summary Vicia faba root meristem cells treated for 24 h with 1.25 mM hydroxyurea and then X-irradiated contained a large number of cells with both chromosome and chromatid aberrations. X-irradiation 4 h after release from the hydroxyurea block yielded cells with almost exclusively chromatid aberrations.Acknowledgments. This paper is based on work performed under contract with the U. S. Energy Research and Development Administration at the University of Rochester Biomedical and Environmental Research Project and has been assigned Report No. UR-3490-443. This work was also partially supported by USPHS, grants FD-00694 and GM-22680.     

Chromosomal abnormalities in starved and marginally malnourished rats and in utero upon rehabilitation

The effects of starvation and marginal malnutrition (MN) on the lymphocytes of rats were evaluated by chromosomal analysis before and after rehabilitation. The effect of parental starvation or malnutrition on chromosomal aberrations in the foetus was also studied. Wistar rats, 30–35 days old, were starved for 5 days or fed a minimally restricted or a severely restricted diet for three weeks. At the end of the period of starvation or malnutrition, lymphocytes were isolated and chromosomal analysis was performed. Starved and severely restricted rats showed significantly higher mean chromosomal aberrations than the controls. These aberrations returned to a normal level when the experimental groups were rehabilitated for a month, indicating that the damage was transient. A chromosomal aberration study done on foetal cells from rehabilitated rats which had previously been starved or fed a severely restricted diet showed significantly increased values, indicating that some damage was permanent. A low number of implantations was also recorded in these experimental groups. These observations clearly indicate that young animals exposed to conditions like starvation or chronic malnutrition are prone to permanent damage of the genetic system.     

Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early, in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocytemacrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of houng adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed, and/or were first to recover, even during continued drug exposure.     

Characterization of murine non-adherent bone marrow cells leading to recovery of endogenous hematopoiesis

Non-adherent bone marrow-derived cells (NA-BMCs) are a mixed cell population that can give rise to multiple mesenchymal phenotypes and that facilitates hematopoietic recovery. We characterized NA-BMCs by flow cytometry, fibroblast colony-forming units (CFU-f), real-time PCR, and in in vivo experiments. In comparison to adherent cells, NA-BMCs expressed high levels of CD11b⁺ and CD90⁺ within the CD45⁺ cell fraction. CFU-f were significantly declining over the cultivation period, but NA-BMCs were still able to form CFU-f after 5 days. Gene expression analysis of allogeneic NA-BMCs compared to bone marrow (BM) indicates that NA-BMCs contain stromal, mesenchymal, endothelial cells and monocytes, but less osteoid, lymphoid, and erythroid cells, and hematopoietic stem cells. Histopathological data and analysis of weight showed an excellent recovery and organ repair of lethally irradiated mice after NA-BMC transplantation with a normal composition of the BM.     

Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice.

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocyte-macrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of young adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed and/or were first to recover, even during continued drug exposure.     

Effect of carbon particles on the recovery of bone marrow stem cells after irradiation in LPS-resistant C3H/HeJ mice

Effect of RES-blockade on bone marrow cells was studied serially after irradiation in LPS-resistant mice. Injection of carbon particles reduced damage and accelerated recovery of marrow hemopoietic stem cells, indicating that LPS-resistant mice can react normally to RES-blockade.     

«Colony-stimulating activity» im Serum und der Milz nach Rauscher Virusinfektion

Summary Colony-stimulating activity (CSA) of serum and spleen was studied in CBA/J mice 1–5 days after Rauscher virus infection, using the agar culture system with normal mouse bone marrow cells as target cells. A sharp increase of CSA was observed with a peak after 2 days in both sites; after 5 days control levels are reached.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft (SFB 112, Zellsystemphysiologie).     

Effect of carbon particles on the recovery of bone marrow stem cells after irradiation in LPS-resistant C3H/HeJ mice

Summary Effect of RES-blockade on bone marrow cells was studied serially after irradiation in LPS-resistant mice. Injection of carbon particles reduced damage and accelerated recovery of marrow hemopoietic stem cells, indicating that LPS-resistant mice can react normally to RES-blockade.This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.     

Radioprotective effect of a protein free parathyroid extract on the mitotic index of rat bone marrow cells.

The protective efficacy of an orally administered bovine protein-free parathyroid extract (PF-PTE) was studied on rat bone marrow cells in vivo with the mitotic index after 850 R irradiation. A remarkable decrease was found in the mitotic activity of bone marrow cells after irradiation in the non-protected animals. However, in the animals treated with PF-PTE after irradiation, a significantly smaller decrease and a faster recovery were found in the mitotic activity of the bone marrow cells.     

The dose-dependence of sister chromatid exchanges induced by 3 hydrocarbons,in the in vivo bone marrow test with Chinese Hamsters

Summary In accordance with their carcinogenic effects, 7, 12-dimethylbenzanthracene and 3,4-benzo(a)pyrene induce sister chromatid exchanges in the bone marrow of Chinese Hamsters in vivo. Phenanthrene is inactive. A dose dependence of induced sister-chromatid exchanges can be shown.Work carried out under Contract No. 022-74-1-ENVD of the E. G. Environmental Research Programme and the Bundesministerium für Forschung und Technologie (Nr. MT 420).     

Cytopathological effects of aristolochic acid on male houseflies causing sterility

Summary Feeding male houseflies with 0.075% aristolochic acid obtained from the plants of the genusAristolochia induced sterility. High condensation of chromosomes, and breakages, have been shown to be responsible for sterility. When onion roots were exposed to aristolochic acid similar chromosomal aberrations were noticed in cells at the tip.Authors are thankful to Prof. Dr G. Rücker (Universität Bonn) for a generous gift of aristolochic acid.     

Radioprotective effect of a protein free parathyroid extract on the mitotic index of rat bone marrow cells

Summary The protective efficacy of an orally administered bovine protein-free parathyroid extract (PF-PTE) was studied on rat bone marrow cells in vivo with the mitotic index after 850 R irradiation. A remarkable decrease was found in the mitotic activity of bone marrow cells after irradiation in the non-protected animals. However, in the animals treated with PF-PTE after irradiation, a significantly smaller decrease and a faster recovery were found in the mitotic activity of the bone marrow cells.     

The protective effect of thiola against the genotoxic action of benzo(a)pyrene

Summary The protective effect of Thiola against the genotoxicity, induced by benzo(a)pyrene, in vitro and in vivo, was investigated. By association of Thiola to benzo(a)pyrene a significant decrease of the numerical and structural chromosome aberrations and a reduction of the incidence of c-mitoses has been obtained in human diploid cells, i.e. human embryonic lung fibroblasts of the cell-line ICP-23, and C₅₆Bl/6 mouse bone marrow cells.