Induction and modulation of lung tumors: Genomic and transcriptional alterations in cigarette smoke-exposed mice
Induction and modulation of lung tumors: Genomic and transcriptional alterations in cigarette smoke-exposed mice
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DOI：
10.1080/01902140490494986
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发表时间：
2005-01-01
影响因子：
1.7
通讯作者：
Balansky, RM
中科院分区：
文献类型：
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作者：
De Flora, S;Izzotti, A;Balansky, RM
香烟烟雾在肺癌的流行病学中起着重要作用，在实验动物的致癌性和化学预防研究中，对烟雾成分进行了广泛的研究。然而，在临床前模型中再现整个复杂混合物的致瘤性要困难得多。作者在此回顾了他们在实验室中获得的一些结果，这些结果涉及烟雾暴露小鼠的肺肿瘤诱导以及基因组和转录改变。作者成功地在4株全身暴露于环境香烟烟雾的小鼠中诱导了肺肿瘤，包括瑞士白化病、A/J、SKH-1无毛和p53突变（UL533 × A/J）F-1小鼠。但所有菌株的致瘤反应均较弱。更强烈的是烟雾引起的各种中间生物标志物的改变，如肺泡巨噬细胞、骨髓和外周血红细胞的细胞遗传终点；支气管上皮细胞凋亡、p53癌蛋白、增殖细胞核抗原；大体积的DNA加合物，8-羟基-2-脱氧鸟苷；多基因表达，以及硫代巴比妥酸反应性醛在全肺和其他器官中的表达。使用巯基n -乙酰半胱氨酸和非甾体抗炎药舒林酸的研究表明，烟雾诱导的基因组和转录改变适合评估化学预防药物对它们的调节作用。
Cigarette smoke plays a major role in the epidemiology of lung cancer, and smoke components have extensively been investigated in carcinogenicity and chemoprevention studies in experimental animals. However, it is much more difficult to reproduce the tumorigenicity of the whole complex mixture, in preclinical models. The authors review here some results obtained in their laboratories, dealing with the induction of lung tumors, and genomic and transcriptional alterations in smoke-exposed mice. The authors were successful in inducing lung tumors in 4 strains of mice exposed whole-body to environmental cigarette smoke, including Swiss albino, A/J, SKH-1 hairless, and p53 mutant (UL533 x A/J)F-1 mice. However the tumor genic response was rather weak in all strains. Much more intense were the smoke-induced alterations of a variety of intermediate biomarkers, such as cytogenetic end points in pulmonary alveolar macrophages, bone marrow, and peripheral blood erythrocytes; apoptosis, p53 oncoprotein, and proliferating cell nuclear antigen in the bronchial epithelium; bulky DNA adducts, 8-hydroxy-2-deoxyguanosine; multigene expression, and thiobarbituric acid-reactive aldehydes in whole lung and several other organs. Smoke-induced genomic and transcriptional alterations were suitable for evaluating their modulation by chemopreventive agents, as shown in studies using the thiol N-acetylcysteine and the nonsteroidal anti-inflammatory drug sulindac.