SELECTIVE 8-HYDROXYGUANINE FORMATION IN PANCREATIC DNA DUE TO A SINGLE INTRAVENOUS ADMINISTRATION OF 4-HYDROXYAMINOQUINOLINE 1-OXIDE IN RATS

被引:15
作者
NAKAE, D [1 ]
ANDOH, N [1 ]
MIZUMOTO, Y [1 ]
ENDOH, T [1 ]
SHIMOJI, N [1 ]
HORIGUCHI, K [1 ]
SHIRAIWA, K [1 ]
TAMURA, K [1 ]
DENDA, A [1 ]
KONISHI, Y [1 ]
机构
[1] NARA MED UNIV,CTR CANC,DEPT ONCOL PATHOL,KASHIHARA,NARA 634,JAPAN
关键词
4-HYDROXYAMINOQUINOLINE; 1-OXIDE; 8-HYDROXYGUANINE; ACINAR CELL NECROSIS; ACINAR CELL CARCINOGENESIS; OXIDATIVE STRESS; RAT;
D O I
10.1016/0304-3835(94)90304-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
8-Hydroxyguanine (8-OHG) formation, a possible initiating event, was determined in pancreatic and liver DNA and compared with the genesis of acinar cell and hepatocyte necrosis in male Wistar rats given a single intravenous administration of 4-hydroxyaminoquinoline 1-oxide (4-HAQO). At the non-necrotic but tumorigenic dose of 7.0 mg/kg body weight, 8-OHG was selectively generated in pancreatic DNA, in the absence of acinar cell necrosis, at the 6 and 24 h time points and repaired by the 48 h time point. When rats were exposed to 4-HAQO at a necrotic dose of 14.0 mg/kg body weight, 8-OHG was also selectively formed in pancreatic DNA with the same time-dependence of generation and repair, while acinar cell necrosis became evident at the 24 h time point and progressed thereafter. Whereas no hepatocyte necrosis was detected in any rats, 8-OHG values for liver DNA merely expressed slight increases only at the 24 and 48 h time points in rats given 14.0 mg/kg body weight of 4-HAQO. The present data suggest that formation of oxidative DNA damage, assayed by 8-OHG, in pancreatic DNA is independent from toxicity and may be involved, along with quinoline adducts, in mutational events underlying 4-HAQO-induced rat acinar cell carcinogenesis.
引用
收藏
页码:97 / 103
页数:7
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