In utero and acute exposure to benzene: Investigation of DNA double-strand breaks and DNA recombination in mice
| Autor: | Christine L. Belanger, Louise M. Winn, Annette Lau |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
DNA damage Health Toxicology and Mutagenesis Bone Marrow Cells Biology medicine.disease_cause law.invention Andrology Mice Bone Marrow Pregnancy law Genetics medicine Animals DNA Breaks Double-Stranded Micronuclei Chromosome-Defective Cell Nucleus Dose-Response Relationship Drug Mutagenicity Tests Benzene DNA medicine.disease Mice Inbred C57BL Leukemia medicine.anatomical_structure In utero Micronucleus test Immunology Recombinant DNA Female Bone marrow Micronucleus Genotoxicity DNA Damage Mutagens |
| Zdroj: | Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 676:74-82 |
| ISSN: | 1383-5718 |
| DOI: | 10.1016/j.mrgentox.2009.04.001 |
| Popis: | Benzene, a ubiquitous pollutant, has been identified as a human leukemogen and early exposure to environmental carcinogens such as benzene has been linked to childhood leukemia. It is known that genotoxic agents can increase the frequency of DNA double-strand breaks (DSBs), which can initiate DNA recombinational repair mechanisms. In this study we investigated the induction of micronuclei, the formation of γ-H2A.X as a marker of DNA DSBs, and the induction of somatic DNA recombination events in hematopoietic tissue from pKZ1 transgenic mice exposed acutely or in utero to benzene. Adult male C57Bl/6N mice were treated with a single i.p. injection of benzene, and timed-pregnant females pKZ1 were treated with daily i.p. injections of 200 mg/kg or 400 mg/kg benzene through gestational days 7–15. Acute exposure to 400 mg/kg benzene resulted in a statistically significant increase in the percentage of micronucleated cells in adult male bone marrow cells and in fetal liver and post-natal day 9 bone marrow cells of mice exposed in utero. Immunoblotting techniques did not detect benzene-induced increases in the formation of γ-H2A.X in bone marrow cells of adult male mice and in maternal bone marrow, fetal liver, and post-natal bone marrow cells after specific time-point exposures. Finally, no recombination events were detected in adult pKZ1 mouse tissue; however, in post-natal day 9 pups in utero exposure to 400 mg/kg of benzene caused a trend towards increasing recombination frequency although this did not reach statistical significance. These results demonstrate that in utero exposure increases the frequency of micronuclei and DNA recombination events in hematopoietic tissue of fetal and post-natal mice and may be an initiating event in the etiology of childhood leukemias. Further investigations into different types of DNA damage and repair pathways are warranted to fully elucidate the role of genotoxic mechanisms in the etiology of benzene-induced childhood leukemias. |
| Databáze: | OpenAIRE |
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