Jones G M, Sanford K K, Parshad R, Gantt R, Price F M, Tarone R E
Br J Cancer. 1985 Oct;52(4):583-90. doi: 10.1038/bjc.1985.230.
The generation of hydrogen peroxide (H2O2) and the derivative free hydroxyl radical (. OH) in cultures of mouse cells grown in the presence of visible light and ambient oxygen was shown previously to be implicated in chromatid damage. Furthermore, chromosome alterations appear to be associated with the spontaneous neoplastic transformation of mouse cells in culture. An attempt was made in this study to reduce the incidence of chromosomal aberrations and delay or prevent the onset of spontaneous neoplastic transformation of freshly isolated mouse cells, both fibroblasts and epidermal keratinocytes, by adding catalase to the culture medium, shielding the cultures from wavelengths less than 500 nm and providing a gas phase of 0-1% O2. These conditions significantly decreased the incidence of chromosomal aberrations in both cell types, and in fibroblasts prevented tumourigenicity in non-irradiated syngeneic mice, and increased latent periods for tumour development in X-irradiated mice. The epidermal keratinocytes were particularly resistant to spontaneous neoplastic transformation under all conditions tested. These observations on the protective effect of extracellular catalase suggest that H2O2, a normal metabolite, and/or the derivative .OH can directly or indirectly produce genetic damage and neoplastic transformation in mouse fibroblasts.
先前的研究表明,在可见光和环境氧气存在的情况下培养的小鼠细胞中,过氧化氢(H2O2)和衍生的游离羟基自由基(·OH)的产生与染色单体损伤有关。此外,染色体改变似乎与培养的小鼠细胞的自发肿瘤转化有关。在本研究中,尝试通过向培养基中添加过氧化氢酶、将培养物与波长小于500nm的光屏蔽以及提供0-1%O2的气相,来降低新鲜分离的小鼠细胞(成纤维细胞和表皮角质形成细胞)的染色体畸变发生率,并延迟或预防自发肿瘤转化的发生。这些条件显著降低了两种细胞类型的染色体畸变发生率,对于成纤维细胞,在未照射的同基因小鼠中预防了致瘤性,并在X射线照射的小鼠中延长了肿瘤发生的潜伏期。在所有测试条件下,表皮角质形成细胞对自发肿瘤转化具有特别的抗性。这些关于细胞外过氧化氢酶保护作用的观察结果表明,正常代谢产物H2O2和/或衍生的·OH可直接或间接在小鼠成纤维细胞中产生遗传损伤和肿瘤转化。