Sakai Ayako, Suzuki Chihiro, Masui Yasuko, Kuramashi Ai, Takatori Kosuke, Tanaka Noriho
Division of Microbiology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Mutat Res. 2007 Jun 15;630(1-2):103-11. doi: 10.1016/j.mrgentox.2007.03.005. Epub 2007 Mar 30.
Cell transformation assays using BALB/3T3 cells can mimic the two-stage process of chemical carcinogenesis in experimental animals. A short-term transformation assay using v-Ha-ras-transfected BALB/3T3 cells (Bhas 42 cells), which was developed by Ohmori et al. and modified by Asada et al., has been reported to detect both tumor initiators and promoters as transformation initiators and promoters, respectively, with their differences based on their protocols. In this new short-term assay, we examined mycotoxins derived from Fusarium and related substances for the initiation and promotion activities of the transformation. The tested substances included deoxynivalenol, nivalenol, fusarenon-X, T-2 toxin, fumonisin B(1), fumonisin B(2), zearalenone, alpha-zearalanol, beta-zearalanol, alpha-zearalenol and beta-zearalenol. Fumonisin B(1) and T-2 toxin were positive for promoting activity in the assay. Especially, T-2 toxin was active at concentrations as low as 0.001-0.002microg/mL in the culture medium. From a comparison between the results of this study and published carcinogenicity assay data, it was expected that the Bhas 42 cell transformation assay had a good correlation with the two-stage carcinogenicity tests using experimental animals for estimation of the tumor-promoting activity.
使用BALB/3T3细胞的细胞转化试验可以模拟实验动物化学致癌作用的两阶段过程。Ohmori等人开发并经Asada等人修改的使用v-Ha-ras转染的BALB/3T3细胞(Bhas 42细胞)的短期转化试验,据报道分别能检测出作为转化引发剂和促进剂的肿瘤引发剂和促进剂,它们的差异基于各自的实验方案。在这个新的短期试验中,我们检测了镰刀菌衍生的霉菌毒素及相关物质对转化的引发和促进活性。所测试的物质包括脱氧雪腐镰刀菌烯醇、雪腐镰刀菌烯醇、镰刀菌烯酮-X、T-2毒素、伏马菌素B(1)、伏马菌素B(2)、玉米赤霉烯酮、α-玉米赤霉醇、β-玉米赤霉醇、α-玉米赤霉烯醇和β-玉米赤霉烯醇。伏马菌素B(1)和T-2毒素在该试验中促进活性呈阳性。特别是,T-2毒素在培养基中低至0.001 - 0.002微克/毫升的浓度下仍具有活性。通过比较本研究结果与已发表的致癌性试验数据,预计Bhas 42细胞转化试验与使用实验动物进行的两阶段致癌性试验在评估肿瘤促进活性方面具有良好的相关性。