Tissue distribution of covalent DNA damage in mice treated dermally with cigarette 'tar': preference for lung and heart DNA.
Tissue distribution of covalent DNA damage in mice treated dermally with cigarette 'tar': preference for lung and heart DNA.
复制标题
用香烟“焦油”进行皮肤处理的小鼠中共价 DNA 损伤的组织分布：对肺和心脏 DNA 的偏好。
DOI：
10.1093/carcin/9.1.75
复制
发表时间：
1988
期刊：
影响因子：
4.7
通讯作者：
Randerath,K
中科院分区：
文献类型：
--
作者：
Randerath,E;Mittal,D;Randerath,K
吸烟者肺癌的高发率被认为与支气管和肺细胞直接暴露于吸入的香烟烟雾中的致癌物质有关。使用a32 P-后标记化学诱导的共价DNA的变化，我们发现，普通的，相对非极性的香烟烟雾成分优先绑定到肺和心脏的DNA在雌性ICR小鼠。在用相当于总共4.5支香烟的香烟烟雾冷凝物（CSC）局部处理6天后，估计肺、心脏、皮肤和肾脏中的共价DNA损伤分别比肝脏中高6.2、5.7、3.9和1.9倍，从肺组织的5.4 ± 0.7 × 106 DNA核苷酸约1个加合物到肝组织的3.3 ± 0.6 × 107 DNA核苷酸约1个加合物。脾脏DNA几乎无内收物。加合物在薄层色谱指纹图谱上占据两个广泛的区域，命名为对角放射性区域（DRZ）1和DRZ 2。在处理1或3天的小鼠中也观察到对肺和心脏DNA的偏好。CSC诱导的共价DNA损伤的组织分布与催化异源生物素（细胞色素P-450单加氧酶，II相酶）和有毒氧物质（超氧化物歧化酶，过氧化氢酶）代谢的酶的活性之间存在负相关。研究结果表明，众所周知的吸烟对健康的不良影响对肺和心血管器官的嗜性，可能部分源于香烟烟雾成分以组织特异性方式诱导肺和心脏DNA损伤的固有能力。可能的机制和健康的影响，推测芳香CSC成分的优先结合肺和心脏DNA进行了讨论。
The high incidence of lung cancer in smokers is thought to be related to the direct exposure of bronchial and pulmonary cells to carcinogens in inhaled cigarette smoke. Using a32P-postlabeling assay for chemically induced covalent DNA alterations, we found that unfractionated, relatively non-polar cigarette smoke components bound preferentially to lung and heart DNA in female ICR mice. After 6 days of topical treatment with cigarette smoke condensate (CSC) equivalent to a total of 4.5 cigarettes, covalent DNA damage was estimated to be 6.2, 5.7, 3.9 and 1.9 times higher, respectively, in lung, heart, skin and kidney than in liver, ranging from approximately 1 adduct in 5.4 ± 0.7 × 106DNA nucleotides in lung to 1 adduct in 3.3 ± 0.6 × 107DNA nucleotides in liver. Spleen DNA was virtually adduct-free. Adducts occupied two extensive zones, designated diagonal radioactive zone (DRZ) 1 and DRZ 2, on TLC fingerprints. Preference for lung and heart DNA was also observed in mice treated for 1 or 3 days. An inverse association appeared to exist between the tissue distribution of CSC-induced covalent DNA damage and the reported activity of enzymes catalyzing the metabolism of xenobiotlcs (cytochrome P-450 monooxygenases, phase II enzymes) and toxic oxygen species (superoxide dismutase, catalase). The results suggest that the well-known pulmonary and cardiovascular organotropism of cigarette-smoking-associated adverse health effects may, in part, have its origin in the inherent capacity of cigarette smoke components to induce lesions in lung and heart DNA in a tissue-specific manner. Possible mechanisms and health implications of the preferential binding of presumably aromatic CSC constituents to lung and heart DNA are discussed.