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学科主题: 公共卫生
题名:
DNA damage triggers imbalance of proliferation and apoptosis during development of preneoplastic foci in the liver of Long-Evans Cinnamon rats
作者: Jia, G; Tohyama, C; Sone, H
关键词: apoptosis ; DNA strand break ; GST-P+ foci ; HCCs ; LEC rat ; p53 ; proliferation
刊名: INTERNATIONAL JOURNAL OF ONCOLOGY
发表日期: 2002-10-01
卷: 21, 期:4, 页:755-761
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: CELL NUCLEAR ANTIGEN ; DOUBLE-STRAND BREAKS ; HEPATOCELLULAR-CARCINOMA ; LEC RATS ; OXIDATIVE STRESS ; COPPER ACCUMULATION ; PLASMA ANTIOXIDANTS ; WILSON-DISEASE ; HEPATITIS ; CARCINOGENESIS
英文摘要:

The mutant strain Long-Evans Cinnamon (LEC) rat accumulates copper, resulting in spontaneous hepatitis and subsequent development of hepatocellular carcinomas (HCCs) in the liver, providing a promising model for investigation of the relationship between hepatitis induced by oxidative stress and hepatocarcinogenesis. We examined DNA strand breaks in peripheral blood cells and p53 expression in livers during acute and chronic hepatitis in LEC rats, along with preneoplastic lesions, and cell proliferation and apoptosis in non-cancerous portions of livers from LEC rats aged 7-115 weeks. Immunohistochemistry using antibodies against glutathione S-transferase placental-form (GST-P), proliferating cell nuclear antigen (PCNA), and in situ DNA nick labeling (TUNEL) were used. Long-Evans Agouti (LEA) rats, a sibling line of the LEC strain, were used as controls. In the LEC rats, DNA strand breaks and expression of p53 were significantly higher than that of LEA rats at 24 weeks of age. The number of GST-P-positive (GST-P+) foci/cm(2) increased and peaked at 48 weeks old, and the areas rapidly expanded thereafter. The level of cell proliferation increased with the development of hepatitis and was highest at about 48 weeks old. The induction of apoptosis in LEC rats was transiently higher than that in LEA rats during the period from 24 to 34 weeks of age. However, the ratio of PCNA-positive cells to the apoptotic index showed a growth imbalance in favor of cell proliferation, supporting sustained net growth in LEC rats. These findings suggest that DNA damage, reflected in DNA strand breaks, plays a critical role in the development of hepatocellular preneoplastic foci, with an imbalance between high proliferation and relatively low apoptosis.

语种: 英语
WOS记录号: WOS:000178162400009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66228
Appears in Collections:北京大学公共卫生学院_期刊论文

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作者单位: 1.Natl Inst Environm Studies, Hlth Effects Res Team, Tsukuba, Ibaraki 3058506, Japan
2.Natl Inst Environm Studies, Environm Hlth Sci Div, Tsukuba, Ibaraki 3058506, Japan
3.Peking Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth Sci, Beijing 100083, Peoples R China

Recommended Citation:
Jia, G,Tohyama, C,Sone, H. DNA damage triggers imbalance of proliferation and apoptosis during development of preneoplastic foci in the liver of Long-Evans Cinnamon rats[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2002,21(4):755-761.
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