Arsenic disrupts cellular levels of p53 and mdm2: A potential mechanism of carcinogenesis
Arsenic disrupts cellular levels of p53 and mdm2: A potential mechanism of carcinogenesis
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DOI：
10.1006/bbrc.1999.1395
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发表时间：
1999-09-24
影响因子：
3.1
通讯作者：
Menzel, DB
中科院分区：
文献类型：
--
作者：
Hamadeh, HK;Vargas, M;Menzel, DB
抗肿瘤蛋白p53在DNA修复中起关键作用。无机砷暴露与多种人类肿瘤，特别是皮肤肿瘤有关。为了研究无机砷如何干扰DNA修复并导致角化过度和皮肤肿瘤的发生率更高，我们将人角质形成细胞（HaCaT）暴露于环境相关浓度的亚砷酸盐中14天。亚砷酸盐降低p53蛋白水平，同时以剂量和时间依赖性方式增加p53调节蛋白mdma水平。我们提出将调节细胞周期停滞的p53-mdm 2环的破坏作为砷相关皮肤致癌作用的模型，这在mdm 2水平升高的肿瘤中可能很重要。(C)北京：科学出版社.
The antitumor protein p53 plays a critical role in DNA repair. Inorganic arsenic exposure is associated with a wide variety of human tumors, particularly of the skin. To investigate how inorganic arsenic might interfere with DNA repair and lead to greater incidence of hyperkeratosis and skin tumors, we exposed human keratinocytes (HaCaT) to environmentally relevant concentrations of arsenite for 14 days. Arsenite reduced p53 levels while concomitantly increasing the p53 regulatory protein mdma levels in a dose- and time dependent manner. We propose the disruption of the p53-mdm2 loop regulating cell cycle arrest as a model for arsenic-related skin carcinogenesis and it may be important in tumors with elevated mdm2 levels. (C) 1999 Academic Press.