期刊
CANCER LETTERS
卷 192, 期 1, 页码 37-47出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0304-3835(02)00685-7
关键词
ethanol; 2-amino-3,8-dimethytimidazo[4,5-f]quinoxaline; rat hepatocarcinogenesis; cell proliferation; 8-hydroxydeoxyguanosine
类别
We investigated promotion potential of ethanol after initiation of hepatocarcinogenesis in male, 21-day-old, F344 rats by exposure to 10 ppm 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline pellet diet for 8 weeks. The rats in group 1 were then fed on liquid control diet for 16 weeks, group 2 receiving the same diet containing 5% ethanol for 8 weeks followed by 8 weeks on the control diet, while group 3 animals were given 5% ethanol containing liquid diet for the entire 16 weeks. On sacrifice at the end of week 24, glutathione S-transferase placental form positive foci, putative preneoplastic lesions in the liver, cell proliferation as indicated by proliferating cell nuclear antigen immunohistochemical staining and levels of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, were significantly increased in the liver of group 3 along with non significant alteration of 8-oxoguanine DNA glycosylase mRNA expression. Lack of persistent increase of above parameters was found in transient ethanol exposure group. These results suggest that chronic consumption of ethanol promotes hepatocarcinogenesis by increasing oxidative stress and cell proliferation. It is also evident that abstinence of ethanol during the second stage stops its persistent promotion effect. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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