Vinblastine treatment induces dose-dependent increases in the frequency of micronuclei in mouse bone marrow

doi:10.1016/0165-1218(92)90003-I

Mutation Research/Genetic Toxicology

Volume 280, Issue 2, August 1992, Pages 87-92

https://doi.org/10.1016/0165-1218(92)90003-I Get rights and content

Abstract

The effect of various doses (0.005–2.0 mg/kg b.w.) of vinblastine sulfate (VBL) was studied on the induction of micronuclei in polychromatic and normochromatic erythrocytes (PCE, NCE) of the bone marrow of female BALB/c mice. VBL treatment resulted in a dose-dependent increase in the frequency of micronucleated PCE and NCE, while the PCE/NCE ratio and mitotic index declined with increasing drug dose. The dose-effect curves were linear quadratic for all the parameters studied.

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Adiponectin (APN) is an adipose tissue-derived cytokine that regulates insulin sensitivity and inflammation. It is also involved in modulation of cell proliferation by binding to various growth factors. Based on its known effects in modulating cell proliferation and oxidative stress, APN may potentially be involved in regulating tissue damage and repair following irradiation. Adiponectin KO mice and their WT littermates were exposed to a single whole-body dose of 3 or 6 Gy gamma radiation. Radiation-induced alterations were studied in jejunum, blood, bone marrow and thymus at days 1 and 5 post-irradiation and compared with sham-irradiated groups. In WT mice, irradiation did not significantly alter serum APN levels while inducing a significant decrease in serum leptin. Irradiation caused a significant reduction in thymocyte cellularity, with concomitant decrease in CD4⁺, CD8⁺ and CD4⁺CD8⁺ T cell populations, with no significant differences between WT and APN KO mice. Irradiation resulted in a significantly higher increase in the frequency of micronucleated reticulocytes in the blood of APN KO compared with WT mice, whereas frequency of micronucleated normochromatic erythrocytes in the bone marrow at day 5 was significantly higher in WT compared with APN KO mice. Finally, irradiation induced similar alterations in villus height and crypt cell proliferation in the jejunum of WT and APN KO mice. Jejunum explants from sham-irradiated APN KO mice produced higher levels of IL-6 compared with tissue from WT animals, but the difference was no longer apparent following irradiation. Our data indicate that APN deficiency does not play a significant role in modulating radiation-induced gastrointestinal injury in mice, while it may participate in regulation of damage to the hematopoietic system.
Effect of vinblastine sulfate on γ-radiation-induced DNA single-strand breaks in murine tissues
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The effect of vinblastine sulfate on γ-radiation-induced DNA strand breaks in different tissues of tumour bearing mice, was studied by single-cell gel electrophoresis. Intraperitonial administration of different doses (0.25–2.0 mg/kg body weight) of vinblastine sulfate 30 min prior to 4 Gy γ-radiation exposure showed a dose-dependent decrease in the yield of DNA strand breaks in murine fibrosarcoma, blood leukocytes and bone marrow cells. The dose-dependent protection of cellular DNA against radiation-induced strand breaks as evidenced from comet tail length, tail moment and percent DNA in the tail, was more pronounced in bone marrow cells than in the cells of the tumor fibrosarcoma. In fibrosarcoma cells, the decrease in comet tail length, tail moment and percent DNA in the tail was detected at lower doses of vinblastine sulfate administration and these parameters were not significantly altered at higher doses, from that of the control irradiated. From this study, it appears that in addition to anticancer activity, vinblastine sulfate could offer protection to the normal tissues against γ-radiation-induced DNA strand breaks.
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The frequency of micronuclei was evaluated in the bone marrow of mice of either sex administered with 0, 0.625, 1.25, 2.5, 5, 10, 20, 40 and 80 mg/kg b.wt of lead nitrate at 12, 24 and 36 h post-treatment. The frequency of micronucleated polychromatic erythrocytes (MPCE) and micronucleated normochromatic erythrocytes (MNCE) increased significantly at 12, 24 and 36 h after treatment with lead nitrate compared to non-drug treated controls. The frequency of micronuclei did not show a dose related increase and the elevation in the frequency of micronuclei was fluctuating type. One important observation which emerged from this study was that the male mice were more sensitive to the induction of micronuclei compared to female mice. This was evidenced by higher frequencies of MPCE in males than females at all the doses for all the post-treatment time periods. The lead nitrate treatment resulted in a spurt in the erythropoiesis as is evidenced by a significant increase in the ratios of polychromatic to normochromatic erythrocytes (P/N ratio) compared to non-drug treated controls at 12, 24 and 36 h post-treatment. The P/N ratio was significantly higher in females than males at 12 and 24 h post-treatment.
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Vinblastine treatment induces dose-dependent increases in the frequency of micronuclei in mouse bone marrow

Abstract

Mutation Res.

Mutation Res.

Mutation Res.

Mutation Res.

Effect of microtubule-associated proteins on the interaction of vincristine with microtubules and tubulin

Cancer Res.

On the use of multiple assays for mutagenicity especially the micronucleus, Salmonella and sperm abnormality assays

The impact of aneuploidy upon public health: mortality and morbidity associated with human chromosome abnormalities

The effect of vincristine on mouse jejunal crypt cells of differing cell age: double labeling autoradiographic studies using 3H and 14C TdR

Cell Tissue Kinet.

Dose response at low doses of X-irradiation and MMS on the induction of micronuclei in mouse erythroblasts

Mutation Res.

Interphase action of vinblastine and vincristine: differences in their lethal actions through the mitotic cycle of cultured mammalian cells

J. Cell Physiol.

The human lymphocytes micronucleus assay: a comparison between whole-blood and separated-lymphocyte cultures

Mutation Res.

Suspect spindle poisons: analysis of c-mitotic effects in mouse bone marrow cells

Mutagenesis

Effect of vincristine on cell survival, cell cycle progression and mitotic accumulation in asychronously growing Sarcoma 180 cells

Cancer Res.

The effect of vincristine on mouse jejunal crypt cells of differing cell age: double labeling autoradiographic studies using ³H and ¹⁴C TdR