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氨基甲酸乙酯诱导的小鼠肺部肿瘤中Ki-67抗原表达与K-ras突变的比较。

Comparison of Ki-67 antigen expression and K-ras mutation in lung tumours induced by urethane in mice.

作者信息

Koohdani F, Sasani F, Mohammad K, Mehdipour P

机构信息

Department of Nutrition and Biochemistry, School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences, Pour Sina Avenue, Tehran 14155-6447, Iran.

出版信息

Singapore Med J. 2009 Jul;50(7):729-33.

Abstract

INTRODUCTION

This study aims to compare Ki-67 antigen expression and K-ras mutation in lung tumours induced by the interfering effects of urethane followed by sodium nitrite, sodium chloride and vitamin D3.

METHODS

The samples were classified into six groups: control (C) group; urethane only (U) group; urethane and vitamin D (U+D) group which received 3.5 mg/kg vitamin D3 for four weeks; urethane and sodium nitrite (U+NS) group which was given sodium nitrite (50 mg/L); urethane and physiological serum (U+NaCl) group; and sodium nitrite and physiological serum (NS+NaCl) group which was given 50 mg/L sodium nitrite and physiological serum, instead of water. The four carcinogen groups receiving urethane were injected intraperitoneally with 600 mg/kg of urethane three times. After 20 weeks of intervention, the mice were killed; the tissues were removed and examined for histopathological changes and comparison of Ki-67 antigen expression and mutations in the exon 1 of the K-ras gene in lung tumours.

RESULTS

There were significant differences in the Ki-67 index between the C group and the U (p-value is less than 0.006, 95 percent confidence interval [CI] -432.9 to -55.6), U+D (p-value is less than 0.05, 95 percent CI -408.3 to -4.6), U+NS (p-value less than 0.02, 95 percent CI -415.7 to -27.2), U+NaCl (p-value less than 0.002, 95 percent CI -478.8 to -90.3) groups. There was no difference between the C and NS+NaC1 groups. There was no mutation in the exon 1 of K-ras gene of the lung tumours.

CONCLUSION

The expression of Ki-67 antigen was found to be increased by urethane in the present study. However, a study on a larger sample size may show anti-tumourogenic effect of vitamin D3. However, the K-ras exon 1 mutations do not play any role in the interfering effects of urethane followed by sodium nitrite and sodium chloride.

摘要

引言

本研究旨在比较氨基甲酸乙酯先后与亚硝酸钠、氯化钠及维生素D3相互作用诱导产生的肺肿瘤中Ki-67抗原表达及K-ras突变情况。

方法

样本分为六组:对照组(C组);仅用氨基甲酸乙酯组(U组);氨基甲酸乙酯与维生素D组(U+D组),接受3.5mg/kg维生素D3,共四周;氨基甲酸乙酯与亚硝酸钠组(U+NS组),给予亚硝酸钠(50mg/L);氨基甲酸乙酯与生理血清组(U+NaCl组);亚硝酸钠与生理血清组(NS+NaCl组),给予50mg/L亚硝酸钠及生理血清而非水。接受氨基甲酸乙酯的四个致癌物组腹腔注射600mg/kg氨基甲酸乙酯,共三次。干预20周后,处死小鼠;取出组织,检查组织病理学变化,并比较肺肿瘤中Ki-67抗原表达及K-ras基因外显子1的突变情况。

结果

C组与U组(p值小于0.006,95%置信区间[CI]-432.9至-55.6)、U+D组(p值小于0.05,95%CI-408.3至-4.6)、U+NS组(p值小于0.02,95%CI-415.7至-27.2)、U+NaCl组(p值小于0.002,95%CI-478.8至-90.3)之间的Ki-67指数存在显著差异。C组与NS+NaCl组之间无差异。肺肿瘤的K-ras基因外显子1未发生突变。

结论

在本研究中发现氨基甲酸乙酯可使Ki-67抗原表达增加。然而,更大样本量的研究可能会显示维生素D3的抗肿瘤作用。但是,K-ras外显子1突变在氨基甲酸乙酯先后与亚硝酸钠和氯化钠的相互作用中不起任何作用。

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