Wolterbeek A P, Roggeband R, van Moorsel C J, Baan R A, Koeman J H, Feron V J, Rutten A A
TNO Nutrition and Food Research Institute, Division of Toxicology, Zeist, The Netherlands.
Cancer Lett. 1995 May 8;91(2):205-14. doi: 10.1016/0304-3835(95)03740-n.
Although most studies concerning the effect of vitamin A and beta-carotene on chemical carcinogenesis are focused on tumour promotion and progression, these compounds may affect initiation as well. In this study the influence of vitamin A and beta-carotene on unscheduled DNA synthesis (UDS) was investigated in hamster tracheal epithelium in organ culture exposed to benzo[a]pyrene (B[a]P). DNA-repair activities were compared with the level of B[a]P-DNA adducts as measured both by 32P-postlabeling and by immunocytochemical detection. In hamster tracheal epithelial cells, both vitamin A and beta-carotene significantly increased B[a]P-induced UDS, with 40% and 45%, respectively. At the same time, vitamin A and beta-carotene decreased the level of B[a]P-DNA adducts in these cells with 18% and 40%, respectively as measured by 32P-postlabeling and with 12% and 35%, respectively as measured by immunocytochemistry. The effect of vitamin A on B[a]P-induced UDS and DNA-adduct levels in hamster tracheal epithelium appeared to depend on the dose of B[a]P vis-à-vis the concentration of vitamin A. The results of the present study show that both vitamin A and beta-carotene cause a decrease in B[a]P-DNA adduct levels by enhancing DNA-repair activities. Because the formation of B[a]P-DNA adducts is considered to be an early step in respiratory tract carcinogenesis, it is suggested that enhancement of DNA-repair activities by vitamin A and the subsequent removal of DNA adducts may be one of the mechanisms involved in vitamin A-mediated protection against cancer.
尽管大多数关于维生素A和β-胡萝卜素对化学致癌作用影响的研究都集中在肿瘤促进和进展方面，但这些化合物也可能影响致癌起始阶段。在本研究中，研究了维生素A和β-胡萝卜素对暴露于苯并[a]芘（B[a]P）的器官培养的仓鼠气管上皮细胞中DNA非程序性合成（UDS）的影响。将DNA修复活性与通过32P后标记法和免疫细胞化学检测法测得的B[a]P-DNA加合物水平进行了比较。在仓鼠气管上皮细胞中，维生素A和β-胡萝卜素均显著增加了B[a]P诱导的UDS，分别增加了40%和45%。同时，通过32P后标记法测得，维生素A和β-胡萝卜素使这些细胞中B[a]P-DNA加合物水平分别降低了18%和40%；通过免疫细胞化学法测得，分别降低了12%和35%。维生素A对仓鼠气管上皮细胞中B[a]P诱导的UDS和DNA加合物水平的影响似乎取决于B[a]P的剂量与维生素A浓度的相对关系。本研究结果表明，维生素A和β-胡萝卜素均通过增强DNA修复活性导致B[a]P-DNA加合物水平降低。由于B[a]P-DNA加合物的形成被认为是呼吸道致癌作用的早期步骤，因此提示维生素A增强DNA修复活性并随后去除DNA加合物可能是维生素A介导的抗癌保护机制之一。
