Department of Therapeutic Radiology, Yale Cancer Center, Yale University School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040, USA.
Exp Biol Med (Maywood). 2011 Oct;236(10):1173-9. doi: 10.1258/ebm.2011.011082. Epub 2011 Aug 15.
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.
癌症患者常存在亚临床维生素 A 缺乏和肺部维生素 A 水平低。既往研究显示，亚临床维生素 A 缺乏会加重大鼠全肺照射诱发的间质性肺炎严重程度。许多研究表明，肺部照射会增加经静脉注入肿瘤细胞后在小鼠肺部形成肿瘤的数目。我们研究了维生素 A 缺乏对正常大鼠和接受过肺照射大鼠源自同源性高转移大鼠横纹肌肉瘤静脉注入肿瘤细胞后肺转移形成的影响。将 WAGrijY 雌性幼鼠随机分为两组，一组给予缺乏维生素 A 和β-胡萝卜素的饮食，另一组给予对照饮食。五周后，缺乏维生素 A 的饮食显著降低了肺和肝脏中视黄醇的水平，但血清中无变化，这与以往亚临床维生素 A 不足患者的研究中观察到的组织和血液水平一致。维生素 A 缺乏饮食未改变未接受照射大鼠静脉注入肿瘤细胞后肺部肿瘤的数目。全肺照射使静脉注入肿瘤细胞后 1 天或 29 天发生的肺部肿瘤数目呈剂量依赖性增加。维生素 A 缺乏未改变这些剂量反应曲线，表明先前在维生素 A 缺乏大鼠中观察到的更为严重的放射性肺炎并未改变全肺照射对转移的增强作用。此外，维生素 A 摄入不足不会影响皮下植入肿瘤的生长，也不会增加源自这些皮下肿瘤的自发性肺转移的数目或大小。因此，尽管低维生素 A 状态会影响肺部损伤的发生，被认为是增加原发性癌症风险的一种可能的可改变危险因素，但在该大鼠模型中，它不会影响皮下肿瘤的生长或增加人工或自发性肺转移的发生。
