Witschi Hanspeter, Espiritu Imelda, Suffia Marie, Pinkerton Kent E
Center for Health and the Environment and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA 95616, USA.
Carcinogenesis. 2002 Feb;23(2):289-94. doi: 10.1093/carcin/23.2.289.
Male strain A mice were fed a diet containing chemopreventive agents. After 1 and 3 weeks on the diets, lung nuclear fractions were examined for expression of cyclin D1/2 with western blot analysis. In animals fed a diet containing a mixture of myoinositol and dexamethasone, a treatment found previously to be effective in preventing the development of tobacco smoke-induced lung tumors in A/J mice, cyclin D1/2 expression was reduced to 30-40% of control levels. A similar decrease in cyclin D1/2 expression was found when animals were fed either myoinositol or dexamethasone alone. Paradoxically, tobacco smoke by itself had a similar effect on cyclin D1/2 expression. On the other hand, several agents that had been previously found not to be effective against tobacco smoke carcinogenesis [phenethyl isothiocyanate, 1,4-phenylenebis(methylene)selenoisocyanate, N-acetylcysteine, acetylsalicylic acid, D-limonene and beta carotene] did not decrease cyclin D1/2 expression after 1 or 3 weeks of feeding. It was concluded that expression of cyclin D1/2 might be a potentially useful marker in the identification of chemopreventive agents for tobacco smoke and could be of some help in the evaluation of their effects.
雄性A品系小鼠喂食含有化学预防剂的饮食。在饮食1周和3周后,通过蛋白质印迹分析检测肺细胞核组分中细胞周期蛋白D1/2的表达。在喂食含有肌醇和地塞米松混合物的饮食的动物中,先前发现该处理可有效预防A/J小鼠中烟草烟雾诱导的肺肿瘤的发生,细胞周期蛋白D1/2的表达降低至对照水平的30%-40%。当动物单独喂食肌醇或地塞米松时,也发现细胞周期蛋白D1/2表达有类似下降。矛盾的是,烟草烟雾本身对细胞周期蛋白D1/2的表达有类似影响。另一方面,几种先前发现对烟草烟雾致癌作用无效的试剂[苯乙基异硫氰酸酯、1,4-亚苯基双(亚甲基)硒异氰酸酯、N-乙酰半胱氨酸、乙酰水杨酸、D-柠檬烯和β-胡萝卜素]在喂食1周或3周后并未降低细胞周期蛋白D1/2的表达。得出的结论是,细胞周期蛋白D1/2的表达可能是鉴定烟草烟雾化学预防剂的潜在有用标志物,并且在评估其效果方面可能有所帮助。