전립선암 세포주에서 방사선에 의한 8-oxoG 축적에 대한 Metallothionein-Ⅲ의 억제효과

Abstract

Metallothioneins (MT) play an important biological role in preventing oxidative damage to cells. We have previously demonstrated that the efficiency of the protective effect of MT-Ⅲ against the DNA degradation from oxidative damage was much higher than that of MT-Ⅰ/Ⅱ. As an extension of the latter investigation, this study aimed to assess the ability of MT-Ⅲ to suppress 8-oxoguanine (8-oxoG), which is one of the major base lesions formed after an oxidative attack to DNA, and the mutant frequency of the hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in human prostate cancer cells, DU145 cells upon exposure to □-rays. We found that human MT-Ⅲ expression decreased the level of 8-oxoG and mutation frequency in the □-irradiated human prostate cancer cells, DU145. Using a 8-oxoguanosine DNA-glycosylase (OGG1)-specific siRNAs, we also found that MT-Ⅲ expression resulted in the suppression of the □-radiation-induced 8-oxoG accumulation and mutation in the OGG1 depleted cells, which is the major repair enzyme of 8-oxoG. Moreover, the down-regulation of MT in cells induced by MT specific siRNA led to a significant increase in the 8-oxoG level, after exposure to □-irradiation. These results suggest that under the conditions of □-ray oxidative stress, MT-Ⅲ prevents the γ-radiation-induced 8-oxoG accumulation and mutation in normal and hOGG1 depleted prostate cancer cells, DU145 and this suppression might, at least in part, contribute to the anticarcinogenic role of MT-Ⅲ.