Goralczyk Regina, Wertz Karin, Lenz Barbara, Riss Georges, Buchwald Hunziker Petra, Geatrix Brad, Aebischer Claude-P, Bachmann Heinrich
Build. 221/106, DSM Nutritional Products Ltd., R and D, Human Nutrition and Health P.O. Box 3255, CH-4002 Basel, Switzerland.
Biochim Biophys Acta. 2005 May 30;1740(2):179-88. doi: 10.1016/j.bbadis.2005.01.005. Epub 2005 Jan 27.
We studied the influence of beta-carotene on the tobacco smoke carcinogen 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor development in the A/J-mouse model. The normally low beta-carotene absorption was facilitated with a diet enriched in fat and bile salt, resulting in plasma and lung tissue levels similar to humans. beta-Carotene enhanced NNK-induced early bronchial cell proliferation, however, this effect was not predictive for later tumor development. Tumor multiplicity was not significantly affected by beta-carotene, neither in carcinogen-initiated nor in uninitiated mice, and regardless of dose and time point of supplementation during tumor development. RARbeta isoform and CYP26 gene expression levels analyzed by quantitative RT-PCR were weakly, but significantly, inversely correlated and showed evidence for altered retinoid signaling and catabolism in the lungs of NNK-initiated, beta-carotene supplemented mice. However, this interaction did not translate into enhanced tumor multiplicity. These results indicate that impaired retinoid signaling is not likely a key factor in lung tumorigenesis in this mouse model.
我们在A/J小鼠模型中研究了β-胡萝卜素对烟草烟雾致癌物4-(N-甲基-N-亚硝基氨基)-1-(3-吡啶基)-1-丁酮（NNK）诱导的肺部肿瘤发生的影响。通过富含脂肪和胆盐的饮食促进了通常较低的β-胡萝卜素吸收，从而使血浆和肺组织水平与人相似。β-胡萝卜素增强了NNK诱导的早期支气管细胞增殖，然而，这种作用并不能预测后期肿瘤的发生。无论是在致癌物启动的小鼠还是未启动的小鼠中，β-胡萝卜素对肿瘤的多发性均无显著影响，且与肿瘤发生过程中补充的剂量和时间点无关。通过定量RT-PCR分析的RARβ亚型和CYP26基因表达水平呈弱但显著的负相关，并且表明在NNK启动、补充β-胡萝卜素的小鼠肺部存在视黄酸信号传导和分解代谢的改变。然而，这种相互作用并未转化为肿瘤多发性的增加。这些结果表明，视黄酸信号传导受损不太可能是该小鼠模型中肺部肿瘤发生的关键因素。
