AntiproliferativeEffect of VitaminA on XenotransplantedCaMa-15 Cells1

In vitro and in vivo investigations have shown that nontoxic treatment with vitamin A (retinol) has an inhibitory effect on the growth of malignant cells. The tumorigenic CaMa-15 cell line responds to both retinol and retinole acid under both anchoragedependent and anchorage-independent conditions, reducing growth or colony formation by at least 50%. To date, there have been few studies on the effects of vitamin A on xenotransplanted neoplastic cells. Twenty-five adult female nude rats (rnu/rnu) were inoculated in the inguinal fat pad with 106 CaMa-15 cells, a tumorigenic epithelial cell line. The rats were divided into three groups: ten high dose (3 mg retinol/day ¡.p.);five low dose (30 u.g retinol/day i.p.); and ten controls (corn oil ¡.p.).All animals were housed in specific-pathogen-free conditions and permitted access to sterile laboratory chow (5.4 /ig retinol/g chow) and water ad libitum. Rats were sacrificed at 21 days after inocula tion. Onset of tumor development occurred between Days 9 and 13 in all groups. Tumors grew progressively and were reduced in mean diameter by 26% (p = <0.05) with high-dose retinol and 44% (p = <0.02) by low-dose treatment. No clinical signs of vitamin A toxicity were apparent. Necropsy and radiological examination revealed no evidence of toxic effects or métastases. These results indicate that vitamin A can reduce the growth of xenotransplanted tumorigenic cells at nontoxic levels in T-celldeficient hosts. The nude rat offers a potential model to study the inhibitory effects of retinoids on xenotransplanted cancers.