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Inhibition by the Dopamine Antagonist Haloperidol of Experimental Carcinogenesis Induced by Azoxymethane in Rat Colon¹

Departments of Gastrointestinal Oncology [H. I., M. B., M. T.], Gastroenterology [S. O.], and Pathology [H. T.], The Center for Adult Diseases, Osaka, 3-3, Nakamichi 1-chome, Higashinari-ku, Osaka 537, Japan

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.

¹ This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy for Cancer Control, Japan.

² To whom requests for reprints should be addressed.

Received 5/14/91. Accepted 9/ 9/91.