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

通过3′-Me-DAB，从封闭的Domyu大鼠群体中培育出抗致癌的DRH大鼠，其肝癌发生过程中肝脏肿瘤的发生率明显低于Donryu大鼠。在此之前，我们观察到DRH大鼠也对舌部4NQO的肿瘤发生表现出一定的抗性。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，关于DRH大鼠除肝脏外其他器官致癌的报道很少。此外，DRH大鼠抗肝癌发生的机制尚不清楚。抑制细胞凋亡可能是致癌的必要因素。本研究旨在探讨细胞凋亡在DRH大鼠癌变抵抗中的作用。我们首先检测了大鼠舌癌发生过程中bcl-2和bax的mRNA水平。虽然DRH大鼠在舌部4NQ0癌变早期表现出一定的抗性，但我们未检测到DRH大鼠与冬玉大鼠之间bcl-2和bax mRNA水平的差异。为了进一步研究DRH大鼠细胞凋亡机制的有效性，我们制备淋巴细胞，在体外用地塞米松或放线菌素d诱导细胞凋亡，检测DNA片段化和bcl-2、bax mrna的表达。我们发现DRH大鼠和Doniyu大鼠在这些估计上存在一些差异。本研究结果提示，两种大鼠的细胞凋亡机制存在一定差异，这可能是DRH大鼠抗癌变的原因

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