Treatment of ethylnitrosourea induced lymphocyte hyperproliferation by DNA hypomethylation in the rat colon

Abstract

N-ethyl-N-nitrosourea (ENU) is a potential carcinogenic agent commonly used in industry, and it may cause an uncontrollable cell proliferation and eventually tumourgenesis. On the other hand, the hypomethilation of DNA by 5-aza-2'-deoxycytidine is the best known antitumoural mechanism used for the treatment of leukemia. Therefore the present study aimed to find out the possible healing effects of 5-aza-2'-deoxycytidine on lymphocyte hyperproliferation in the rat colon through the above mentioned DNA hypomethylation mechanism. Rats were injected with 300mg/kg body weight - body weight ENU (i.p.) in order to induce tumour development. Following 45 weeks when the tumourgenesis was proved visually, animals were treated with 5-aza-2'-deoxycytidine 100μg/100 g body weight twice a week intraperitoneally for 15 weeks. After the experimental procedure, all animals were sacrificed and colonal tissues were obtained. Tissues were processed for light and electron microscopy. While no colonal tumour development was observed in the control group, an extensive tumour development was seen in the subcutaneous region in the high dose ENU treated group. The light and electron microscopical examination of the rat colonal tissue revealed a lymphocyte hyperproliferation and invasion in the submucosal region, an increased number of polimorphonuclear leukocytes (PMNLs) and occasional epithelial lesions. On the other hand, the evaluation of the 5-aza-2'-deoxycytidine treatment group rat colon demonstrated features similar to those seen in the control and PEG treated groups indicating a possible anti-neoplastic effect of 5-aza-2'-deoxycytidine via DNA hypomethylation.