亚硝基脲对DNA损伤作用的研究进展

Progress in DNA Damage Induced by Nitrosoureas

亚硝基脲是重要的抗癌烷化剂,应用于多种恶性肿瘤的临床治疗。亚硝基脲分解生成活泼亲电中间体而与生物大分子作用,导致DNA碱基烷化、互补碱基对横向交联等损伤,最终诱导癌细胞凋亡而发挥其抗癌作用。由于亚硝基脲在动物实验和临床应用中表现出的复杂生理活性,有关亚硝基脲对DNA损伤作用机制的研究,已成为该类药物设计开发以及癌症防治领域中的热点问题。本文对近年来国内外有关亚硝基脲对DNA损伤作用机制的研究进行了综述。

Nitrosoureas are significant anticancer alkylating agents and generally applied for the clinical treatment of a variety of human malignancies. Nitrosoureas undergo decomposation and generate active electrophilic intermediates to react with biological macromolecules. These reactions can lead to DNA alkylation and interstrand cross-links of complementary base pairs, which finally result in apoptosis of cancer cells so as to exert anticancer activity of the drugs. Nitrosoureas show complicated physiological activity in animal experiments and clinical application. Consequently, the mechanism of DNA damage induced by nitrosoureas has become a hot issue in the field of antineoplastic drug design and cancer prevention. In this paper, the studies of the DNA damage mechanism by nitrosourcas in recent years are reviewed.