Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos.
Asbestos and man-made-mineral fibers are known to increase one type of oxidative DNA damage, 8-hydroxyguanine (8-OH-(Gua), in vitro. In this study, we analyzed the 8-OH-Gua level in DNA and its repair activity after a single intratracheal instillation of fibers (crocidolite or glass) or saline to Syrian hamsters or Wistar rats. The 8-OH-Gua level was measured with a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) system. The 8-OH-Gua repair enzyme activity was determined with an endonuclease nicking assay using a 32P-labeled or fluorescently labeled 22mer DNA that contains 8-OH-Gua at a specific position. A significant increase in the 8-OH-Gua level in the lung DNA was observed 1 day after the exposure to crocidolite, as compared to the saline control. The repair activity was increased significantly at 7 days. On the other hand, after exposure to glass fibers, little or no increase of these carcinogenicity indicators was detected. These assays of 8-OH-Gua and its repair activity in short-term animal experiments will be useful for evaluating the carcinogenicity of fibers. This is the first report of the increase of 8-OH-Gua and its repair activity in the animal lung after the instillation of asbestos fibers.
Yamaguchi
R
R
Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyusyu, Japan.
Hirano
T
T
Ootsuyama
Y
Y
Asami
S
S
Tsurudome
Y
Y
Fukada
S
S
Yamato
H
H
Tsuda
T
T
Tanaka
I
I
Kasai
H
H
D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D006224:Cricetinae; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004260:DNA Repair; D005898:Glass; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D017638:Asbestos, Crocidolite; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA