Rodent carcinogenesis bioassay with oxisuran, a selective immunosuppressive agent

Abstract

The carcinogenic potential of oxisuran, a synthetic immunosuppressive agent, was studied for 80 weeks and 104 weeks in mice and rats, respectively. Groups of 50 mice and 70 rats of each sex received oxisuran at doses of 600, 240, and 40 mg/kg/day as dietary admixtures over the entire experimental period. Adequate survival rates allowed accurate statistical analysis of diagnosed neoplasia. Increased susceptibility to tumor development was not clearly demonstrated. In mice the only statistically significant increase in the incidence of malignancy was lung carcinomas in high dose females ( P < 0.05). However, lung carcinoma incidence was significantly decreased in mid- and low-dose male mice when compared to spontaneous control rates ( P < 0.01). Although not confirmed statistically, there was an increased incidence of lung carcinomas and liver cell adenomas in high dose male mice, and increased lymphoid tumors in all female treated groups. In rats, the incidence of liver cell adenomas in high dose animals of both sexes was increased, although confirmed statistically in males only ( P < 0.01). In high dose females, significantly decreased incidences of mammary fibroadenomas, pituitary chromophobe adenomas, and thyroid parafollicular cell tumors ( P < 0.01) contributed to an overall decrease in both benign tumors and in the combined benign and malignant tumor rates.