Dietary exposure to diesel exhaust particles and oxidatively damaged DNA in young oxoguanine DNA glycosylase 1 deficient mice.
Pulmonary exposure to diesel exhaust particles (DEP) has been associated with high levels of oxidized DNA in lung cells, whereas long-term oral DEP exposure appears to induce the DNA repair system with concomitant unaltered levels of oxidized DNA in the colon and liver of rats. Here we studied the generation of oxidatively damaged DNA in young wild type (WT) and oxoguanine DNA glycosylase 1 (OGG1) deficient mice after dietary exposure to 0mg/kg, 0.8 mg/kg, or 8 mg/kg Standard Reference Material 1650 in the feed for 21 days. The ingestion of DEP did not increase the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine and comet assay endpoints in terms of strand break, endonuclease III, and formamidopyrimidine glycosylase (FPG) in the colon, liver, and lung tissue of WT or Ogg1(-/-) mice. The level of OGG1 mRNA could only be measured in WT mice and it was not increased by DEP feeding. On the contrary, the level of FPG sites was twofold higher in the liver and lung of Ogg1(-/-) mice compared to the levels in the WT mice tissues. In conclusion, although Ogg1(-/-) mice have high levels of oxidized guanine lesions, they do not appear to be markedly vulnerable to the genotoxicity by oral administration of DEP.
Risom
Lotte
L
Institute of Public Health, Department of Occupational and Environmental Health, University of Copenhagen, Øster Farimagsgade 5, DK-1014 Copenhagen K, Denmark.
Møller
Peter
P
Dybdahl
Marianne
M
Vogel
Ulla
U
Wallin
Håkan
H
Loft
Steffen
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases / Q000172:deficiency* / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004032:Diet; D008099:Liver / Q000187:drug effects / Q000196:embryology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
D012333:RNA, Messenger; D001335:Vehicle Emissions; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D003849:Deoxyguanosine