Monoamine oxidase B inhibitor enhances experimental carcinogenesis in rat colon induced by azoxymethane.
The effects of prolonged administration of the monoamine oxidase (MAO)-A inhibitor N-methyl-N-propargyl-3-(2,4-dichlorophenoxy)propylamine (clorgyline) and the MAO-B inhibitor N-methyl-N-2-propynyl-benzylamine (pargyline) 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 investigated in Wistar rats. Rats were treated s.c. with 7.4 mg/kg body weight of 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 increased the incidence of colon tumors in week 35. However, it did not influence the histological appearance of the colon tumors or the histological types and depth of involvement of colon adenocarcinomas. Furthermore, it significantly increased the NE concentration in the colon wall and the labeling index of the colon mucosa during and after AOM-treatment. 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 carcinogenesis, and that its effect may be related to its effect in increasing the NE concentration in the colon wall and subsequently increasing the proliferation of colon epithelial cells.
Iishi
H
H
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Tatsuta
M
M
Baba
M
M
Taniguchi
H
H
D000818:Animals; D001397:Azoxymethane; D003010:Clorgyline / Q000633:toxicity*; D003106:Colon / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D004357:Drug Synergism; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D010293:Pargyline / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D010293:Pargyline; D003010:Clorgyline; D001397:Azoxymethane; D009638:Norepinephrine