Micronuclei, DNA single-strand breaks and DNA-repair activity in mice exposed to 1,3-butadiene by inhalation.
We investigated single-strand breaks and endonuclease III-sensitive sites in DNA along with gamma-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/m3) 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 gamma-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 gamma-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).
Vodicka
Pavel
P
Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic. pvodicka@biomed.cas.cz
Stetina
Rudolf
R
Smerak
Petr
P
Vodickova
Ludmila
L
Naccarati
Alessio
A
Barta
Ivo
I
Hemminki
Kari
K
D000280:Administration, Inhalation; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002070:Butadienes / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology; D029968:Escherichia coli Proteins / Q000378:metabolism; D005720:Gamma Rays; D022781:Hepatocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective; D012044:Regression Analysis
D002070:Butadienes; D029968:Escherichia coli Proteins; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; C031763:1,3-butadiene