Target organ-specific covalent DNA damage preceding diethylstilbestrol-induced carcinogenesis.
Target organ-specific covalent DNA damage preceding diethylstilbestrol-induced carcinogenesis.
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己烯雌酚诱发癌变之前的靶器官特异性共价 DNA 损伤。
DOI：
10.1093/carcin/6.7.1067
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发表时间：
1985
期刊：
影响因子：
4.7
通讯作者：
Randerath,E
中科院分区：
文献类型：
--
作者：
Liehr,JG;Randerath,K;Randerath,E
合成雌激素己烯雌酚（DES），一种已知的人类致癌物质，在雄性叙利亚仓鼠中，在皮下注射后6个月内诱导肾癌。置入肿瘤的形成可能是由其激素特性或反应性遗传毒性代谢物结合DNA引起的，但以前的尝试检测加合物失败了。在本研究中，雄性叙利亚仓鼠的肾脏DNA，用s.c.应用32 P-后标记法分析DES诱导的加合物的存在。共价修饰的DNA核苷酸在慢性DES治疗后的肾脏中检测到，但在未治疗的仓鼠的肾脏中，或在DES治疗的动物的肝脏或肿瘤组织中未检测到。本报告首次证明了雌激素在体内特异性地在致癌靶器官中引起共价DNA修饰的能力。DES诱导的共价DNA加合物被认为是DES通过损伤细胞大分子引发肿瘤的证据，除了先前描述的肿瘤促进作用之外。
The synthetic estrogen diethylstilbestrol (DES), a known human carcinogen, induces renal carcinoma in male Syrian hamsters within 6 months after s.c. implantation. Tumor formation could be evoked by its hormonal properties or by a reactive genotoxic metabolite binding to DNA, but previous attempts to detect adducts have failed. In the present study, kidney DNA of male Syrian hamsters, treated with s.c. DES implants to induce renal carcinoma, was analyzed for the presence of DESinduced adducts using32P-postlabeling assay. Covalently-modified DNA nucleotides were detected in the kidneys after chronic DES treatment, but not in kidneys of untreated hamsters, or in liver or tumor tissue of DEStreated animals. This report demonstrates for the first time the ability of an estrogen to give rise to covalent DNA modificationin vivospecifically in the target organ of carcinogenesis. DES-induced covalent DNA adducts are taken as evidence for tumor initiation by DES via damage to cellular macromolecules, in addition to tumor-promotional effects described previously.