Effect of OK-432 on large-bowel carcinogenesis in rats

To examine the carcinogenetic and growth inhibitory effects of OK-432, large-bowel carcinoma was induced experimentally in rats by intrarectal injection of N-methyl-N-nitrosourea (MNU), and OK-432 was administered intradermally. Rats were sacrificed after six months and the large intestine was cut into serial sections. Histopathologic examination and analysis of the infiltrating mononuclear cells, using monoclonal antibodies, were performed. The average rate of carcinogenesis per rat was 15.7 +/- 8.5 in the MNU alone group (n = 10) and 8.3 +/- 3.5 in the MNU and OK-432 group (n = 6). The invasion was deeper than the muscularis propria in 16 out of 157 lesions (10.2 percent) in the MNU alone group and in one out of 50 lesions in the MNU + OK-432 group (2.0 percent) (P less than 0.05). When time of appearance of atypical glands or carcinomas were compared in the MNU alone and MNU + OK-432 group, carcinogenesis was found to be delayed in the MNU + OK-432 group. In the investigation of infiltrating mononuclear cells using monoclonal antibodies, there were increases in helper T cells in both the MNU alone and MNU + OK-432 groups, but there was little difference between the two groups. The results of this study suggest that the suppression of experimental carcinogenesis in the large bowel by the concomitant administration of OK-432 with MNU, may be due to the enhanced activation or prolonged activated state of immunocompetent cells, which appear via antigen recognition, by OK-432.