Beta-adrenergic modulation of NNK-induced lung carcinogenesis In hamsters
Beta-adrenergic modulation of NNK-induced lung carcinogenesis In hamsters
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DOI：
10.1007/pl00008474
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发表时间：
2000-11-01
影响因子：
3.6
通讯作者：
Riechert, A
中科院分区：
文献类型：
--
作者：
Schuller, HM;Porter, B;Riechert, A
目的：肺癌是工业化国家癌症死亡的主要原因。肺腺癌（PAC）是最常见的肺癌组织学类型，烟草特有的亚硝胺4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（NNK）可在实验室啮齿动物中重复诱发PAC。我们最近已经表明，来源于人PAC的细胞系的生长受β-肾上腺素能受体控制，并且NNK是该受体家族的高亲和力激动剂。设计图：在本研究中，我们使用完善的NNK诱导的PAC仓鼠模型测试了这些体外结果与体内NNK诱导的肺肿瘤发生的相关性。结果如下：我们的实验表明，在长期暴露于β-肾上腺素能激动剂肾上腺素或茶碱的动物中，NNK诱导的PAC多样性显著增加，这导致β-肾上腺素能第二信使cAMP的细胞内积累。另一方面，我们的数据显示，在每次NNK注射之前给予β-肾上腺素能拮抗剂普萘洛尔显著抑制PAC的发展。讨论内容：我们的研究结果支持这一假设，即烟草相关PAC的发展可能受到β-肾上腺素能药物的调节，并且NNK与β-肾上腺素能受体的相互作用有助于这种组织学肺癌类型的发生。
Objective: Lung cancer is the leading cause of cancer death in industrialized countries. Pulmonary adenocarcinoma (PAC) is the most common histologic type of lung cancer, and it is reproducibly induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in laboratory rodents. We have recently shown that the growth of cell lines derived from human PACs is controlled by beta -adrenergic receptors, and that NNK is a high affinity agonist for this receptor family. Design: In the current study, we have tested the relevance of these in in vitro findings for in vivo NNK-induced lung tumorigenesis, using a well-established hamster model of NNK-induced PAC. Results: Our experiments demonstrate a significant increase in NNK-induced PAC multiplicity in animals chronically exposed to the beta -adrenergic agonist epinephrine or theophylline which causes intracellular accumulation of the beta -adrenergic second messenger cAMP. On the other hand, our data show that administration of the beta -adrenergic antagonist propranolol prior to each NNK injection significantly inhibited the development of PACs. Discussion: Our findings support the hypothesis that the development of tobacco-associated PAC may be modulated by beta -adrenergic agents, and that the interaction of NNK with beta -adrenergic receptors contributes to the genesis of this histologic lung cancer type.