Association of carcinogen-resistant mechanisms of the inbred rat strain DRH with apoptosis

近交系大鼠DRH抗癌机制与细胞凋亡的关系

• 批准号: 13672135
• 负责人: MIURA Masayoshi
• 金额: $ 1.79万
• 依托单位: Fukuoka Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672135/
• 关键词: Apoptosis; carcinogenesis; carcinogenesis

A carcinogen-resistant inbred strain DRH rat developed from a closed colony of Domyu rats shows a remarkably low incidence of liver tumors during hepatocarcinogenesis by 3'-Me-DAB compared with Donryu rats.. Previously, we observed that DRH rats had also showed some resistance against tumorigenesis by 4NQO in the tongue. Recently, some genes have been reported which may be responsible for the resistance against hepatocarcinogenesis in DRH rats. However, there have been few reports on carcinogenesis in organs of DRH rats other than the liver. Furthermore, the mechanisms of resistance against hepatocarcinogenesis in DRH rats are not known.Suppression of apoptosis may be a factor required for carcinogenesis. The purpose of the present study is to investigate the participation of apoptosis in resistance against carcinogenesis in DRH rats. We first examined mRNA levels of bcl-2 and bax during carcinogenesis in the rat tongue. Although DRH rats showed some resistance in the early stage of carcinogenesis in the tongue by 4NQ0, we could detect no difference in the levels of bcl-2 and bax mRNA between DRH and Dontyu rats.To further study the effectiveness of mechanisms of apoptosis in DRH rats, lymphocytes were prepared and apoptosis was induced in vitro by Dexamethasone or Actinomycin D. Then, DNA fragmentation and expression of bcl-2 and bax mRNAs were estimated. We detected some differences in those estimations between DRH and Doniyu rats.The present results suggest that there exists some difference in the mechanisms of apoptosis in the two rat strains, which may be responsible for the resistance of DRH rats against carcinogenesis

从一个封闭的Domyu大鼠群中培育出的致癌物抗性近交系DRH大鼠显示，与Donryu大鼠相比，在3 '-Me-DAB诱发肝癌期间，肝肿瘤的发生率显著降低。以前，我们观察到DRH大鼠也表现出对舌中4 NQO的肿瘤发生的一些抵抗。近年来，一些基因被报道可能与DRH大鼠抗肝癌发生有关。然而，很少有关于DRH大鼠肝脏以外器官致癌的报道。此外，DRH大鼠对肝癌发生的抵抗机制尚不清楚，细胞凋亡的抑制可能是肝癌发生所必需的因素。本研究的目的是探讨细胞凋亡在DRH大鼠抗肿瘤发生中的作用。我们首先检测了大鼠舌癌发生过程中bcl-2和bax的mRNA水平。DRH大鼠对4 NQ_0诱发的舌癌有一定的抵抗作用，但bcl-2和bax mRNA的表达水平与Dontyu大鼠无明显差异。然后，DNA片段化和bcl-2和bax mRNA的表达进行了估计。DRH大鼠与Doniyu大鼠在上述指标上存在差异，提示DRH大鼠与Doniyu大鼠在细胞凋亡机制上存在差异，这可能是DRH大鼠抗肿瘤作用的重要机制之一