Prevention of cigarette smoke-induced lung tumors in mice by budesonide, phenethyl isothiocyanate, and N-acetylcysteine
Prevention of cigarette smoke-induced lung tumors in mice by budesonide, phenethyl isothiocyanate, and N-acetylcysteine
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DOI：
10.1002/ijc.24942
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发表时间：
2010-03-01
影响因子：
6.4
通讯作者：
De Flora, Silvio
中科院分区：
文献类型：
--
作者：
Balansky, Roumen;Ganchev, Gancho;De Flora, Silvio
肺癌是世界范围内肿瘤性疾病中最重要的死亡原因，而香烟烟雾（CS）是癌症的主要危险因素。作为避免暴露于CS的补充，化学预防将降低被动吸烟者、戒烟者和戒烟成瘾的当前吸烟者的癌症风险。不幸的是，化学预防临床试验产生了令人失望的结果，直到最近，一个合适的动物模型评估CS致癌性是不可用的。我们以前证明，主流CS诱导一个强大的致癌反应时，暴露的小鼠从出生开始。在本研究中，新生小鼠（品系H）暴露于CS连续120天，从出生开始。根据各种方案口服化学预防剂布地奈德（2.4 mg/kg饮食）、苯乙基异硫氰酸酯（PEITC，1，000 mg/kg饮食）和N-乙酰基-L-半胱氨酸（NAC，1，000 mg/kg体重）。实验在210天后停止。暴露于CS导致良性肺肿瘤的高发病率和多样性，恶性肺肿瘤和其他组织病理学改变的显着增加。所有三种化学预防剂，目前吸烟者断奶后，是相当有效的保护配偶和雌性小鼠CS肺致癌性。当给予戒烟者停止接触CS后，布地奈德的保护能力没有改变，而PEITC失去了部分癌症化学预防活性。总之，所提出的实验模型提供了令人信服的证据，它是可能的，以防止CS诱导的肺癌通过饮食和药物。
Lung cancer is the most important cause of death among neoplastic diseases worldwide, and cigarette smoke (CS) is the major risk factor for cancer. Complementarity to avoidance of exposure to CS, chemoprevention will lower the risk of cancer in passive smokers, ex-smokers, and addicted current smokers who fait to quit smoking. Unfortunately, chemoprevention clinical trials have produced disappointing results to date and, until recently, a suitable animal model evaluating CS carcinogenicity was not available. We previously demonstrated that mainstream CS induces a potent carcinogenic response when exposure of mice starts at birth. In the present study, neonatal mice (strain H) were exposed to CS for 120 consecutive days, starting at birth. The chemopreventive agents budesonide (2.4 mg/kg diet), phenethyl isothiocyanate (PEITC, 1,000 mg/kg diet), and N-acetyl-L-cysteine (NAC, 1,000 mg/kg body weight) were administered orally according to various protocols. The experiment was stopped after 210 days. Exposure to CS resulted in a high incidence and multiplicity of benign lung tumors and in significant increases of malignant lung tumors and other histopathological alterations. All three chemopreventive agents, administered to current smokers after weaning, were quite effective in protecting both mate and female mice from CS pulmonary carcinogenicity. When given to ex-smokers after withdrawal of exposure to CS, the protective capacity of budesonide was unchanged, while PEITC lost part of its cancer chemopreventive activity. In conclusion, the proposed experimental model provides convincing evidence that it is possible to prevent CS-induced lung cancer by means of dietary and pharmacological agents.