Abstract
Cancer patients often have subclinical vitamin A deficiencies and low vitamin A lung levels. Previous studies showed that subclinical vitamin A deficiency increased the severity of pneumonitis induced by whole-lung irradiation in rats. Many studies have shown that lung irradiation increases the number of lung tumors developing from intravenously injected tumor cells in mice. We examined the impact of vitamin A deficiency on the development of lung metastases from a highly metastatic syngeneic rat rhabdomyosarcoma in normal rats and rats receiving prior lung irradiation. Weanling female WAGrijY rats were randomized to receive either a diet lacking both vitamin A and beta-carotene or a control diet. After five weeks, the deficient diet significantly decreased levels of retinol in the lung and liver but not in the serum, modeling the tissue and blood levels seen in prior studies of patients with subclinical vitamin A inadequacy. The vitamin A-deficient diet did not alter the number of lung tumors developing from intravenously injected tumor cells in unirradiated rats. Whole-lung irradiation produced dose-dependent increases in the number of lung tumors developing from tumor cells injected intravenously one or 29 d after irradiation. Vitamin A deficiency did not alter these dose-response curves, indicating that the more intense radiation-induced pneumonitis seen previously in vitamin A-deficient rats did not alter the enhancement of metastases produced by whole-lung irradiation. Moreover, inadequate vitamin A intake did not influence the growth of tumors implanted subcutaneously or increase the number or size of the spontaneous lung metastases developing from these subcutaneous tumors. Thus, although low vitamin A status influences the development of lung injury and is considered a possible modifiable risk factor increasing risk of primary cancer, it did not affect the growth of subcutaneous tumors or increase the development of artificial or spontaneous lung metastases in this rat model.