Inhibition by the dopamine antagonist haloperidol of experimental carcinogenesis induced by azoxymethane in rat colon.
The effects of the dopamine agonist bromocriptine and antagonist haloperidol on the incidence and histology of colon tumors induced by azoxymethane and on the labeling index of colon mucosa were investigated in Wistar rats. Rats received weekly s.c. injections of 7.4 mg/kg of body weight azoxymethane for 10 weeks and s.c. injections of 2 mg/kg of body weight bromocriptine or 2 mg/kg of body weight haloperidol, in depot form, every other day until the end of the experiment in week 30. Administration of haloperidol resulted in a significant decrease in the incidence of colon tumors. It also caused a significant decrease in the incidence of adenocarcinomas, with 75% of the tumors being adenomas, and in the labeling index of the colon epithelial cells. In contrast, bromocriptine had no influence on the incidence or histology of colon tumors or the labeling index of the colon mucosa. These findings indicate that the dopamine antagonist haloperidol inhibits colon carcinogenesis and that this effect may be related to its effect in decreasing the proliferation of colon epithelial cells.
Iishi
H
H
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Baba
M
M
Tatsuta
M
M
Okuda
S
S
Taniguchi
H
H
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D001835:Body Weight; D001971:Bromocriptine / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D000242:Cyclic AMP / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D018492:Dopamine Antagonists; D002149:Energy Intake; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D008940:Mitotic Index; D051381:Rats; D011919:Rats, Inbred Strains
D018492:Dopamine Antagonists; D001971:Bromocriptine; D004247:DNA; D000242:Cyclic AMP; D006220:Haloperidol; D001397:Azoxymethane