Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, 984388 Nebraska Medical Center, Omaha, NE 68198-4388, USA.
Int J Mol Sci. 2021 Jul 30;22(15):8238. doi: 10.3390/ijms22158238.
This article reviews evidence suggesting that a common mechanism of initiation leads to the development of many prevalent types of cancer. Endogenous estrogens, in the form of catechol estrogen-3,4-quinones, play a central role in this pathway of cancer initiation. The catechol estrogen-3,4-quinones react with specific purine bases in DNA to form depurinating estrogen-DNA adducts that generate apurinic sites. The apurinic sites can then lead to cancer-causing mutations. The process of cancer initiation has been demonstrated using results from test tube reactions, cultured mammalian cells, and human subjects. Increased amounts of estrogen-DNA adducts are found not only in people with several different types of cancer but also in women at high risk for breast cancer, indicating that the formation of adducts is on the pathway to cancer initiation. Two compounds, resveratrol, and -acetylcysteine, are particularly good at preventing the formation of estrogen-DNA adducts in humans and are, thus, potential cancer-prevention compounds.
这篇文章综述了一些证据，这些证据表明一种常见的起始机制会导致许多常见类型的癌症的发生。内源性雌激素以儿茶酚雌激素-3,4-醌的形式在癌症起始的这个途径中发挥核心作用。儿茶酚雌激素-3,4-醌与 DNA 中的特定嘌呤碱基反应，形成使嘌呤脱失的雌激素-DNA 加合物，从而产生无嘌呤位点。然后，无嘌呤位点可能导致致癌突变。已经使用试管反应、培养的哺乳动物细胞和人体的结果证明了癌症起始的过程。不仅在患有几种不同类型癌症的人群中，而且在乳腺癌高危人群中也发现了大量的雌激素-DNA 加合物，这表明加合物的形成是癌症起始途径的一部分。两种化合物，白藜芦醇和乙酰半胱氨酸，特别擅长于防止人类形成雌激素-DNA 加合物，因此是潜在的癌症预防化合物。
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