Possible Role of K-ras Oncogene in Mutagenic Activity of Ethylnitrosourea on Lymphocyte Hyperproliferation in Rat Colon

Abstract

N-ethyl-N-nitrosourea (ENU) is a potential carcinogenic agent that is commonly used in industry. Therefore the present study aimed to find out the possible effects of this agent on the rat digestive tract especially on the colon. We have studied the complementary mutation activity of the exon 2 of K-ras oncogene by ENU treatment in rat colonal tissue. While the two experimental group rats were injected once a week with 20 mg/kg and 300 mg/kg body weight-body weight with ENU (i.p.), the last experimental group was administered only with PEG and the control group animals received no treatment. Following 45 weeks, all animals were sacrificed and colonal tissues were obtained. Tissues were processed for light and electron microscopy and also for molecular biological analyses. While no colonal tumour development was observed in the control and in the PEG treated group, an extensive tumour development was seen in a wide range of tissues in the high dose ENU treated group. The light and electron microscopical examination of the rat colonal tissue revealed a lymphocyte hyperproliferation in the submucosal region, an increased number of polymorphonuclear leukocytes (PMLs) and occasional epithelial lesions. The mutation analyses of exon 2 of K-ras by HpaII demonstrated more than one recognition sites in the ENU treated group whereas there was only one enzyme cognate site in the control group.