Oxidative DNA damage in vitamin C-supplemented guinea pigs after intratracheal instillation of diesel exhaust particles.
The health effects of diesel exhaust particles (DEP) are thought to involve oxidative damage. We have investigated the effect of intratracheal DEP instillation to guinea pigs in three groups of 12 animals each given 0, 0.7, or 2.1 mg. Five days later guinea pigs exposed to DEP had increased levels of oxidized amino acids (gamma-glutamyl semialdehyde), DNA strand breaks, and 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in the lung. Bulky DNA ad- ducts were not significantly elevated in the lung. The antioxidant enzyme activity of glutathione reductase was increased in the lung of DEP-exposed guinea pigs, whereas glutathione peroxidase and superoxide dismutase enzyme activities were unaltered. There was no difference in DNA strand breaks in lymphocytes or urinary excretion of 8-oxodG at the two doses tested. Protein oxidations in plasma and in erythrocytes were not altered by DEP exposure. The concentrations of ascorbate in liver, lung, and plasma were unaltered by the DEP exposure. The results indicate that in guinea pigs DEP causes oxidative DNA damage rather than bulky DNA adducts in the lung. Guinea pigs, which are similar to humans with respect to vitamin C metabolism, may serve as a new model for the study of oxidative damage induced by particulate matter.
Møller
Peter
P
Institute of Public Health, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
Daneshvar
Bahram
B
Loft
Steffen
S
Wallin
Håkan
H
Poulsen
Henrik E
HE
Autrup
Herman
H
Ravn-Haren
Gitte
G
Dragsted
Lars O
LO
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism* / Q000494:pharmacology; D004249:DNA Damage / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007442:Intubation, Intratracheal; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
D001335:Vehicle Emissions; D001205:Ascorbic Acid