Micronuclei, DNA single-strand breaks and DNA-repair activity in mice exposed to 1,3-butadiene by inhalation

• Published in: Mutation research Vol. 608; no. 1; pp. 49 - 57
• Main Authors: Vodicka, Pavel, Stetina, Rudolf, Smerak, Petr, Vodickova, Ludmila, Naccarati, Alessio, Barta, Ivo, Hemminki, Kari
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 19-09-2006; Elsevier
• Subjects: 1,3-Butadiene; Administration, Inhalation; Animals; Biological and medical sciences; Bone Marrow Cells - cytology; Butadienes - administration & dosage; Butadienes - blood; Butadienes - toxicity; Comet Assay; Deoxyribonuclease (Pyrimidine Dimer) - metabolism; DNA Damage; DNA Repair; DNA-repair activity; Erythrocytes - cytology; Escherichia coli Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gamma Rays; Genetics of eukaryotes. Biological and molecular evolution; Hepatocytes - metabolism; Male; Medical sciences; Mice; Micronuclei, Chromosome-Defective; Micronucleus formation; Regression Analysis; Single-strand DNA breaks; Toxicology; DNA-repair activity; 1,3-Butadiene; Micronucleus formation; Single-strand DNA breaks; Mutagenicity testing; Rodentia; Inhalation; Vertebrata; Toxicology; Mammalia; Single strand break; Mouse; DNA; Micronucleus; Genetics; Repair
• ISSN: 1383-5718; 0027-5107; 1879-3592
• DOI: 10.1016/j.mrgentox.2006.05.003

We investigated single-strand breaks and endonuclease III-sensitive sites in DNA along with γ-irradiation-specific DNA-repair activity in hepatocytes and frequencies of micronuclei in polychromatic bone-marrow erythrocytes of male NMRI mice (2 months old, weight 30–35
g) during sub-acute inhalation exposure to 1,3-butadiene (28 days, 500
mg/m
3) and up to 28 days after the exposure. Concentrations of 1,3-butadiene in blood, an indicator of internal exposure, moderately increased during the exposure period. The most interesting finding was that γ-irradiation-specific DNA-repair activity gradually increased during exposure, being significantly higher compared with control levels on days 7 and 28 of exposure (
P
=
0.005 and 0.035, respectively), reaching a maximum on day 1 after the termination of exposure (
P
=
0.003) and then returning to control levels. A significant correlation between γ-irradiation-specific DNA-repair activity and the concentration of 1,3-butadiene in blood (
R
=
0.866,
P
=
0.050) supports a possible induction of DNA-repair activity by the exposure to 1,3-butadiene and formation of its metabolites. The initial increase in micronucleus frequency (micronuclei per 1000 cells) in the exposed mice continuously decreased from 20.4
±
5.1 (day 3) to 15.1
±
3.2 (day 28) within the exposure period, and subsequently from 12.4
±
5.1 to 4.6
±
1.6 in the period following termination of the 1,3-butadiene exposure, while micronucleus frequencies in control animals were significantly lower (from 1.7
±
1.5 to 4.2
±
0.8).