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Journal of Cancer Prevention

Original Article

Cancer prevention research 2008; 13(4): 336-343

Published online December 30, 2008

© Korean Society of Cancer Prevention

Time Course Study of the Changes in Leukocytic and Colonocytic DNA Damage and Preneoplastic Aberrant Crypt Foci of DMH-induced Colon Carcinogenesis in F344 Rats

Eunju Park1, Gyeong-Im Jeon1 and Kyung-Hea Lee2


Colon cancer is one of the leading causes of death in both men and women not only in Western countries also in some Asian countries including Korea. Experimental colon carcinogenesis is a multistep process involving three distinct stages, initiation, which alters the DNA coding information of a normal cell, followed by promotion and progression, which ultimately result in a phenotypically altered transformed cell. Rat colon carcinogenesis model using 1,2-dimethylhydrazine (1,2-DMH) and using preneoplastic aberrant crypt foci (ACF) as endpoint marker lesions have been used to assess the influence of modulatory factors on colon cancer. To understand the changes in DNA damage in leukocytes and colonocytes and preneoplastic ACF during colon carcinogenesis, F344 male rats were given subcutaneous injection of 1,2-DMH (30 mg/kg body weight) once a week for a period of 6 weeks and sacrificed every 4 week for 40 weeks. The body weight and the relative weights of organs to body weight of DMH injected group were significantly lower than the saline injected normal control group. The number of AC or ACF per colon substantially increased from 76 at 4th to 215 at 40th for ACF and from 170 to 839 for AC throughout the experimental period. DMH induced DNA damage in colonocytes increased significantly at 8, 24, 28, 32th week compared to the normal control, while DNA damage in leukocytes increased at 8, 24th week. These results will provide a better understanding of colon carcinogenesis induced by DMH (180 mg/kg body weight) in F344 rats and also prevention strategies by bioactive substances. (Cancer Prev Res 13, 336-344, 2008)

Keywords: Colon cancer, 1,2-Dimethyhydrazine, Aberrant crypt foci, DNA damage, Comet assay, F344 rat

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