Increased 8-hydroxyguanine levels in DNA and its repair activity in rat kidney after administration of a renal carcinogen, ferric nitrilotriacetate

被引:80
作者
Yamaguchi, R
Hirano, T
Asami, S
Chung, MH
Sugita, A
Kasai, H
机构
[1] UNIV OCCUPAT & ENVIRONM HLTH,DEPT ENVIRONM ONCOL,YAHATANISHI KU,KITAKYUSHU,FUKUOKA 807,JAPAN
[2] UNIV OCCUPAT & ENVIRONM HLTH,DEPT UROL,YAHATANISHI KU,KITAKYUSHU,FUKUOKA 807,JAPAN
[3] SEOUL NATL UNIV,COLL MED,DEPT PHARMACOL,SEOUL 110799,SOUTH KOREA
关键词
D O I
10.1093/carcin/17.11.2419
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The renal carcinogen, ferric nitrilotriacetate (Fe-NTA), is known to induce oxidative stress and the subsequent formation of a type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), in the rat kidney (Umemura et al., 1990). Using an improved DNA isolation method (Nakae et al., 1995), which reduces the background level of 8-OH-Gua, we found a five-fold increase in the 8-OH-Gua level in kidney DNA after a single i.p. injection of Fe-NTA. On the basis of the report that 8-OH-Gua repair activity is enhanced after cells are exposed to oxidative stress due to ionizing radiation (Bases et al., 1992), the measurement of 8-OH-Gua repair activity will also be useful to assess cellular oxidative stress, The 8-OH-Gua repair enzyme activity was determined,vith an endonuclease assay using a 22 mer DNA that contains 8-OH-Gua at a specific position, A five-fold increase in the 8-OH-Gua repair activity as compared with the control, was observed in the target organ, the rat kidney, 120 h after Fe-NTA administration, In the non-target organ, the liver, the increase was not as large (two-fold), This simple assay of oxidative DNA damage repair will be useful for evaluating the carcinogenicity of oxygen radical forming chemicals, in addition to chemical analyses of oxidative DNA damage.
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页码:2419 / 2422
页数:4
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