Changes of 8-OH-dG levels in DNA and its base excision repair activity in rat lungs after inhalation exposure to hexavalent chromium.
According to the toxicological and epidemiological studies, hexavalent chromium (Cr) is associated with increase of lung cancer risk. Genotoxic effects, such as chromosomal aberrations, and cellular oxidative DNA damage by reactive oxygen species produced by hexavalent Cr exposure may play an important role in its carcinogenesis. To clarify whether reactive oxygen species are involved in its mechanism, we examined the levels of 8-hydroxydeoxyguanine (8-OH-dG) and its base excision repair activities in the lung tissues of rats that repeatedly inhaled a sodium chromate solution mist for 1, 2, and 3 weeks. The levels of 8-OH-dG increased significantly in the lung tissues of the rats exposed for 1 week at the low concentration (0.18 mg/m(3), P<0.05), as compared with the controls. However, there was no difference in the 8-OH-dG levels at the higher concentration or with more than 2 weeks of exposure. The 8-OH-dG repair activities decreased in a dose-dependent manner during 2 weeks of exposure, on the contrary they recovered at 3 weeks of repeated exposure. These results suggest that the DNA damage caused by hexavalent Cr inhalation is induced by the generation of reactive oxygen species and by inhibition of base excision repair activity during the earlier phase of exposure. However, the 8-OH-dG levels and its repair activities recovered to the level of the controls in the latter inhalation exposure period.
Maeng
Seung-Hee
SH
Center for Occupational Toxicology, Occupational Safety & Health Research Institute, Korea Occupational Safety & Health Agency, Daejeon 305-380, South Korea.
Chung
Hai-Won
HW
Yu
Il-Je
IJ
Kim
Hyeon-Yeong
HY
Lim
Cheol-Hong
CH
Kim
Kwang-Jong
KJ
Kim
Soo-Jin
SJ
Ootsuyama
Yuko
Y
Kasai
Hiroshi
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002840:Chromates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017670:Sodium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D013997:Time Factors
D002840:Chromates; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; C028982:sodium chromate(VI); D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine