DNA DAMAGE MEASURED BY COMET ASSAY AND 8-OH-dG FORMATION RELATED TO BLOOD CHEMICAL ANALYSES IN AGED RATS
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概要
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To evaluate the effects of aging on DNA damage, spontaneous and chemical-induced DNA damage and its repair were examined using comet assays at pH 9, 12.1 and 13, and an 8-OH-dG assay in the liver and kidney of young (9-week-old) and aged (20-month-old) rats. Additionally, blood chemistry was examined to investigate any correlation between vital functions and age-dependent DNA damage. DNA migration at pH 13 and 8-OH-dG levels increased in the liver and/or kidney of aged rats, but DNA migration did not increase at pH 9 or 12.1; that is, alkali-labile sites and 8-OH-dG were concomitantly accumulated in aged rats. These results suggest that 8-OH-dG production caused by reactive oxygen species exceeded glycosylation and that the glycosylation activity is far more than the AP endonucleation in aged rats. Methyl methanesulfonate (MMS, 80 mg/kg, i.p.) increased DNA migration at pH 12.1 and 13 in the liver and kidney at 3 and 24 hr after treatment in young and aged rats. The DNA dam- age in aged rats was less and decreased more slowly compared with young rats. The pictures of MMS-induced DNA migrations at pH 12.1 and 13 were very similar to each other. These results suggest that the adduct glycosylation and repair of the single-strand breaks (SSBs) of aged rats are less than those of young rats, although AP endonucleation is sufficient to remove the AP sites. N-nitrosodiethylamine (160 mg/kg, i.p.) increased DNA migration at pH 12.1 and 13 in the liver and kidney at 3 and 24 hr in young rats and at pH 12.1 and 13 in the kidney at 24 hr in aged rats. These results showed that SSBs were predominantly detected as chemical-induced DNA damage and DNA repairs such as N-glycosylase, DNA polymerase and DNA ligase, and that the metabolic activation declined in aged rats. Aspartate aminotransferase, alanine aminotransferase, total bilirabin, total cholesterol, total protein, globulin, creatinine and chloride age-dependently increased and alkaline phosphates, albumin/globulin ratio, inorganic phosphorus and potassium age-dependently decreased, and these changes were correlated with the DNA migration at pH 13 and/or 8-OH-dG. These results suggest that the activity of DNA repair and metabolic activation enzymes declines in aged rats and that the accumulation of spontaneous DNA damage may affect vital functions.
- 日本トキシコロジー学会の論文
- 2007-08-17
著者
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Sato Itaru
Department of Veterinary Medicine, Faculty of Agriculture, Iwate University
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Tsuda Shuji
Department of Veterinary Medicine, Faculty of Agriculture, Iwate University
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Takasaki Wataru
Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.
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HASHIMOTO Kazuyuki
Department of Pediatrics, Graduate School of Medicine, Gifu University
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Sato Itaru
Laboratory Of Veterinary Public Health Department Of Veterinary Medicine Faculty Of Agriculture Iwat
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Sato Itaru
Department Of Applied Veterinary Science The Doctoral Course Of The United Graduate School Of Veteri
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Sato Itaru
Department Of Applied Chemistry Faculty Of Science Science University Of Tokyo
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Tsuda Shuji
Department Of Veterinary Medicine Faculty Of Agriculture Iwate University
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Tsuda Shuji
Department Of Applied Veterinary Science The Doctoral Course Of The United Graduate School Of Veteri
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Tsuda S
Lab. Of Veterinary Public Health Dep. Of Veterinary Medicine Fac. Of Agriculture Iwate Univ.
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Takasaki Wataru
Medicinal Safety Laboratories Daiichi Sankyo Co. Ltd.
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Takasaki Wataru
Medicinal Safety Research Labs. Daiichi Sankyo Co. Ltd.
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Takasaki Wataru
Analytical And Metabolic Research Laboratories Sankyo Co. Ltd.
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Takasaki Wataru
Pharmaceutical Institute Tohoku University
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Takasaki W
Medicinal Safety Research Labs. Daiichi Sankyo Co. Ltd.
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Hashimoto Kazuyuki
Department Of Applied Veterinary Science The Doctoral Course Of The United Graduate School Of Veteri
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Hashimoto Kazuyuki
Department of Applied Veterinary Science, The Doctoral Course of the United Graduate School of Veterinary Science, Gifu University:Laboratory of Veterinary Public Health, Department of Veterinary Medicine, Faculty of Agriculture, Iwate University:Medicina
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