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Induction of micronuclei by vinyl acetate in mouse bone marrow cells and cultured human lymphocytes
Abstract:
A dose-dependent increase in micronucleated polychromatic erythrocytes was observed in the bone marrow of male C57B1/6 mice 30 h after a single intraperitoneal injection of vinyl acetate (250, 500, 1000 or 2000 mg/kg b.wt.; (9-14 animals per group). The effect was statistically significant at 1000 mg/kg (1.33 +/- 0.29% vs. 0.6 +/- 0.10% in olive oil-treated controls) and at 2000 mg/kg (1.57 +/- 0.19%) of vinyl acetate. These doses were fatal to 6 (1000 mg/kg) and 8 (2000 mg/kg) out of 14 animals in both groups. The ratio of polychromatic to normochromatic cells decreased as a function of vinyl acetate dose. Cyclophosphamide (20 mg/kg), used as a positive control chemical, induced a clear increase in micronucleated polychromatic erythrocytes (2.07 +/- 0.20%). None of the treatments affected the number of micronuclei in normochromatic erythrocytes. In human whole-blood lymphocyte cultures, micronucleus induction by a 48-h treatment with vinyl acetate (0.125, 0.25, 0.5, 1 and 2 mM; 24 h after culture initiation) was studied in lymphocytes with preserved cytoplasm from smear slides prepared by a method involving the removal of erythrocytes at harvest by sodium cyanide treatment to improve preparation quality. The frequency of micronucleated lymphocytes reached a peak at 0.5 mM (3.2 +/- 1.0% vs. 0.9 +/- 0.1% in control cultures) and 1 mM (3.1 +/- 0.7%), with a decline at 2 mM probably because of a toxic effect resulting in mitotic inhibition.
Insights
Vinyl acetate exposure increased micronuclei in mouse bone marrow and human lymphocytes, indicating genotoxicity. Higher doses proved toxic, causing fatalities in mice and reduced cell division in human cultures.
Area of Science:
- Toxicology
- Genetics
- Cell Biology
Background:
- Vinyl acetate is an industrial chemical with potential health risks.
- Genotoxicity testing is crucial for assessing chemical safety.
- Micronucleus assays are standard methods for detecting chromosomal damage.
Purpose of the Study:
- To evaluate the genotoxic potential of vinyl acetate in vivo and in vitro.
- To determine the dose-response relationship of vinyl acetate-induced genotoxicity.
- To assess the toxicity and effects on cell division.
Main Methods:
- In vivo micronucleus test in male C57B1/6 mice bone marrow after intraperitoneal injection.
- In vitro micronucleus test in human whole-blood lymphocyte cultures.
- Analysis of micronucleated polychromatic erythrocytes and lymphocyte frequencies.
- Assessment of cell toxicity and mitotic inhibition.
Main Results:
- Vinyl acetate caused a dose-dependent increase in micronucleated polychromatic erythrocytes in mice.
- Significant genotoxic effects were observed at 1000 and 2000 mg/kg in mice, with high mortality.
- In human lymphocytes, vinyl acetate induced micronuclei peaking at 0.5 and 1 mM, with toxicity at 2 mM.
Conclusions:
- Vinyl acetate exhibits genotoxic activity in both mammalian and human cell systems.
- The compound demonstrates dose-dependent toxicity, impacting cell viability and division.
- Further investigation into vinyl acetate's long-term health effects is warranted.