Chemical Division, Kanagawa Prefectural Institute of Public Health, Chigasaki 2530087, Japan.
Research Initiatives and Promotion Organization, Yokohama National University, Yokohama 2408501, Japan.
Int J Mol Sci. 2022 Mar 16;23(6):3216. doi: 10.3390/ijms23063216.
The Bhas 42 cell transformation assay (Bhas 42 CTA) is the first Organization for Economic Cooperation and Development (OECD)-certificated method used as a specific tool for the detection of the cell-transformation potential of tumor-promoting compounds, including non-genotoxic carcinogens (NGTxCs), as separate from genotoxic carcinogens. This assay offers the great advantage of enabling the phenotypic detection of oncotransformation. A key benefit of using the Bhas 42 CTA in the study of the cell-transformation mechanisms of tumor-promoting compounds, including non-genotoxic carcinogens, is that the cell-transformation potential of the chemical can be detected directly without treatment with a tumor-initiating compound since Bhas 42 cell line was established by transfecting the v-Ha- gene into a mouse fibroblast cloned cell line. Here, we analyzed the gene expression over time, using DNA microarrays, in Bhas 42 cells treated with the tumor-promoting compound 12--tetradecanoylphorbol-13-acetate (TPA), and NGTxC, with a total of three repeat experiments. This is the first paper to report on gene expression over time during the process of cell transformation with only a tumor-promoting compound. Pathways that were activated or inactivated during the process of cell transformation in the Bhas 42 cells treated with TPA were related not only directly to but also to various pathways in the hallmarks of cancer.
Bhas 42 细胞转化分析（Bhas 42 CTA）是第一个获得经济合作与发展组织（OECD）认证的方法，可作为检测肿瘤促进化合物（包括非遗传毒性致癌剂（NGTxCs））转化潜能的特定工具，与遗传毒性致癌剂分开。该方法具有能够检测肿瘤转化表型的巨大优势。在研究肿瘤促进化合物（包括非遗传毒性致癌剂）的细胞转化机制时使用 Bhas 42 CTA 的一个主要优点是，可以直接检测化学物质的细胞转化潜力，而无需用肿瘤起始化合物进行处理，因为 Bhas 42 细胞系是通过将 v-Ha-基因转染到小鼠成纤维细胞克隆细胞系中建立的。在这里，我们使用 DNA 微阵列分析了 Bhas 42 细胞在肿瘤促进化合物 12--十四烷酰佛波醇-13-乙酸酯（TPA）和 NGTxC 处理下随时间的基因表达，总共进行了三个重复实验。这是第一篇仅用肿瘤促进化合物报告细胞转化过程中随时间变化的基因表达的论文。在 TPA 处理的 Bhas 42 细胞中，细胞转化过程中激活或失活的途径不仅与直接相关，还与癌症特征中的各种途径相关。
