Changes in levels of 8-hydroxyguanine in DNA, its repair and OGG1 mRNA in rat lungs after intratracheal administration of diesel exhaust particles.
Diesel exhaust particles (DEP), an environmental pollutant, are known to induce lung cancer in experimental animals. To clarify whether reactive oxygen species (ROS) are involved in its carcinogenic mechanism, we examined the levels of 8-hydroxyguanine (8-OH-Gua), its total repair and the repair enzyme OGG1 mRNA in female Fischer 344 rat lungs, as markers of the response to ROS, after DEP was intratracheally instilled. The 8-OH-Gua levels in both DEP-treated groups (2 and 4 mg) were increased during the 2-8 h following exposure to DEP. The 8-OH-Gua repair activities in the DEP-treated groups decreased during the period from 2 h to 2 days following DEP exposure and then recovered to the level of the control group at 5 days after exposure. OGG1 mRNA was induced in rats treated with 4 mg DEP for 5-7 days after administration. In conclusion, the 8-OH-Gua level in rat lung DNA increases markedly at an early phase after DEP exposure, by the generation of ROS and the inhibition of 8-OH-Gua repair activity, and induction of OGG1 mRNA is also a good marker of cellular oxidative stress during carcinogenesis.
Tsurudome
Y
Y
Department of Environmental Oncology and Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences and Department of Biochemistry and Department of Surgery 1, School of Medicine, Onogawa, Tsukuba, Ibaraki 305-0053, Japan.
Hirano
T
T
Yamato
H
H
Tanaka
I
I
Sagai
M
M
Hirano
H
H
Nagata
N
N
Itoh
H
H
Kasai
H
H
D000818:Animals; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D001335:Vehicle Emissions / Q000633:toxicity*
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase