MECHANISMS OF OXIDATIVE DAMAGE INDUCED P53 MUTATIONS

关键靶基因的突变，例如肿瘤抑制基因p53， 是人类癌症发展的重要一步。尽管 这些突变的原因在许多情况下是未知的，有很多证据 提示由活性氧引起的DNA损伤可能是 在一些人类肿瘤中，一个重要的致突变DNA损伤来源， 包括乳腺癌。我们建议研究“氧化DNA” 利用分子流行病学的方法，提出损伤假说。使用双氧水- LMPCR和H_2O_2诱导的损伤/修复分布 恒变性毛细管电泳法检测突变热点 利用HPRT的几个外显子，获得相同靶细胞的靶基因 培养的人TK6细胞基因作为可选择的靶基因。数据 从这些研究中积累起来的可能会为我们提供对分子 提供证据说明乳腺癌发生的机制 支持初步迹象表明氧化DNA损伤在 在人乳腺上皮肿瘤转化中的作用。

Mutation of Critical Target Genes, e.g., the tumor suppressor gene p53, are an important step in the development of human cancers. Although the causes of these mutations are in many instances unknown, much evidence suggests that DNA damage induced by reactive oxygen species (ROS) may be an important source of promutagenic DNA damage in some human neoplasms, including breast cancer. We propose to investigate the 'oxidative DNA damage hypothesis' using the molecular epidemiology approach. Using H2O2- induced damage/repair distributions by LMPCR and the H2O2-induced mutational hotspots by constant denaturant capillary electrophoresis in a target gene of identical target cells, using several exons of the HPRT gene of cultured human TK6 cells as a selectable target gene. The data accrued from these studies may provide insight into the molecular mechanisms involved in breast cancer development by providing evidence supporting the preliminary indications that oxidative DNA damage plays a role in the neoplastic transformation of human breast epithelium.