MONOAMINE-OXIDASE-B INHIBITOR ENHANCES EXPERIMENTAL CARCINOGENESIS INRAT COLON INDUCED BY AZOXYMETHANE

The effects of prolonged administration of the monoamine oxidase (MAO) -A inhibitor hyl-N-propargyl-3-(2,4-dichlorophenoxy)propylamine (clorg yline) and the MAO-B inhibitor N-methyl-N-2-propynyl-benzylamine (parg yline) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on the norepinephrine (NE) concentration in the colon wall and the labeling index of colon mucosa were investigat ed in Wistar rats. Rats were treated s.c. with 7.4 mg/kg body weight o f AOM once a week for 10 weeks, and also s.c. with 5 mg/kg body weight of clorgyline or 50 mg/kg body weight of pargyline in 0.9% NaCl until the end of the experiment. Treatment with pargyline significantly inc reased the incidence of colon tumors in week 35. However, it did not i nfluence the histological appearance of the colon tumors or the histol ogical types and depth of involvement of colon adenocarcinomas. Furthe rmore, it significantly increased the NE concentration in the colon wa ll and the labeling index of the colon mucosa during and after AOM-tre atment. In contrast, clorgyline had no influence on the development or histological appearance of colon tumors. These findings indicate that the MAO-B inhibitor, but not the MAO-A inhibitor, enhanced colon carc inogenesis, and that its effect may be related to its effect in increa sing the NE concentration in the colon wall and subsequently increasin g the proliferation of colon epithelial cells.