Chemoprevention of smoke-related DNA adduct formation in rat lung and heart.
Chemoprevention of smoke-related DNA adduct formation in rat lung and heart.
复制标题
化学预防大鼠肺和心脏中与烟雾相关的 DNA 加合物形成。
DOI：
10.1093/carcin/13.11.2187
复制
发表时间：
1992
期刊：
影响因子：
4.7
通讯作者：
S. De Flora
中科院分区：
文献类型：
--
作者：
Alberto Izzotti;R. Balansky;N. Coscia;L. Scatolini;F. D'Agostini;S. De Flora
采用同步荧光分光光度法（SFS）检测了132份雄性SD大鼠组织中苯并[a]芘二醇环氧（BPDE）-DNA加合物的形成及其化学预防作用。每组6只动物全身暴露于主流香烟烟雾中，每天一次，连续40天。肝脏DNA中没有发现加合物，而肺中从暴露的第8天开始检测到与烟雾相关的DNA加合物，并持续增加，直到第40天。在暴露28天和40天后监测的心脏DNA加合物达到的水平甚至高于在同一动物肺部检测到的水平。在这两个器官中测量的与烟雾相关的DNA加合物的量之间存在高度相关性。巯基N-乙酰基-L-半胱氨酸（NAC），一种有效的突变和癌症化学预防剂，以前已被证明可以抑制大鼠接受苯并[a]芘的气管内滴注形成的SFS阳性DNA加合物，每天通过灌胃给药，显着防止发生相同的加合物在烟雾暴露的大鼠的心脏和肺。在假暴露动物的肝脏、肺或心脏DNA中未观察到荧光信号。该分子剂量测定研究的结果补充了对来自相同大鼠的组织和细胞进行的平行组织病理学、细胞遗传学、生物化学和代谢分析的结果，为暴露于香烟烟雾产生的各种显著改变和NAC的特定保护作用提供了证据。
The formation of smoke-related DNA adducts and their chemoprevention were investigated in tissues of male Sprague-Dawley rats, by testing a total of 132 DNA samples by synchronous fluorescence spectrophotometry (SFS), which mainly detects benzo[a]pyrene diolepoxide (BPDE)-DNA adducts. Groups of six animals each were exposed whole-body to mainstream cigarette smoke, once daily, for up to 40 consecutive days. No adduct was revealed in liver DNA, whereas smoke-related DNA adducts were detectable in the lung from the 8th day of exposure and continued to increase until the 40th day. Adducts to heart DNA, which were monitored after 28 and 40 days of exposure, attained even higher levels than those detected in the lungs of the same animals. A high correlation existed between the amounts of smoke-related DNA adducts measured in these two organs. The daily administration by gavage of the thiol N-acetyl-L-cysteine (NAC), an effective mutation and cancer chemopreventive agent, which had been previously shown to inhibit the formation of SFS-positive DNA adducts in rats receiving intratracheal instillations of benzo[a]pyrene, significantly prevented occurrence of the same adducts in both heart and lungs of smoke-exposed rats. No fluorescence signal was observed in liver, lung, or heart DNA of sham-exposed animals. The findings of this molecular dosimetry study complement the results of parallel histopathologic, cytogenetic, biochemical and metabolic analyses of tissues and cells from the same rats, providing evidence for a variety of significant alterations produced by exposure to cigarette smoke and for the specific protective role of NAC.