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

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Singapore Med J 2009; 50(7): 729-733
Comparison of Ki-67 antigen expression and K-ras mutation in lung tumours induced by urethane in mice

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Koohdani F, Sasani F, Mohammad K, Mehdipour P
Correspondence: Dr Fariba Koohdani, fkoohdan@sina.tums.ac.ir

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 (50mg/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.

Keywords: carcinogens, K-ras genes, Ki-67 antigen, lung tumour, vitamin D, urethane
Singapore Med J 2009; 50(7): 729-733

http://smj.org.sg/sites/default/files/5007/5007a12.pdf
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