Ueno Y, Habano W, Yamaguchi H, Masuda T, Morimura S, Nemoto K, Kojima S, Tashiro F
Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Food Chem Toxicol. 1991 Sep;29(9):607-13. doi: 10.1016/0278-6915(91)90142-t.
The transforming activity of luteoskyrin (LS), a bis-anthraquinoid mycotoxin produced by Penicillium islandicum Sopp., and a hepatocarcinogen in rodents, was examined by an in vitro transformation assay using mouse embryonal Balb/3T3 A31-1-1 cells. The results revealed that LS induced type III foci at 0.5 micrograms/ml, and that the cells selected from these foci by soft-agar cloning grew with a high saturation density. Thus, it was confirmed that LS not only induces hepatic tumours in laboratory animals, but also transforms in vitro cultured mammalian cells. The tumorigenicity of the transformants obtained was confirmed by transplantation into nude mice and by image analysis with IIIIn. A transfection assay, using calcium phosphate co-precipitation, demonstrated that the DNA of the cloned cells transformed NIH3T3 cells. Northern blot also revealed transcriptional activation of c-myc and c-Ha-ras oncogenes. The possible participation of LS-derived hydroxy radicals in the formation of genetic lesions was discussed.
岛青霉产生的双蒽醌类霉菌毒素黄天精（LS）具有致癌性，可诱发啮齿动物肝癌。本研究采用小鼠胚胎Balb/3T3 A31-1-1细胞体外转化试验检测了LS的转化活性。结果显示，LS在浓度为0.5微克/毫升时可诱导III型集落形成，且通过软琼脂克隆从这些集落中筛选出的细胞具有高饱和密度生长特性。因此，证实了LS不仅可在实验动物中诱发肝肿瘤，还能使体外培养的哺乳动物细胞发生转化。通过移植到裸鼠体内以及使用IIIIn进行图像分析，证实了所获得的转化细胞具有致瘤性。利用磷酸钙共沉淀法进行的转染试验表明，克隆细胞的DNA可转化NIH3T3细胞。Northern印迹分析还显示c-myc和c-Ha-ras癌基因的转录激活。文中讨论了LS衍生的羟基自由基在遗传损伤形成过程中的可能作用。
