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


CONCLUSIONS
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.
Koohdani
F
F
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. fkoohdan@sina.tums.ac.ir
Sasani
F
F
Mohammad
K
K
Mehdipour
P
P
D000818:Animals; D002762:Cholecalciferol / Q000378:metabolism; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012965:Sodium Chloride / Q000737:chemistry; D012977:Sodium Nitrite / Q000737:chemistry; D014520:Urethane / Q000633:toxicity*; D014807:Vitamin D / Q000737:chemistry; D018631:ras Proteins / Q000096:biosynthesis*
D019394:Ki-67 Antigen; D014807:Vitamin D; D002762:Cholecalciferol; D014520:Urethane; D012965:Sodium Chloride; D018631:ras Proteins; D012977:Sodium Nitrite