German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.
Toxicol In Vitro. 2019 Sep;59:55-63. doi: 10.1016/j.tiv.2019.04.008. Epub 2019 Apr 8.
The human breast epithelial cell lines MCF-10A and MCF-12A form well-differentiated acinus-like structures when grown in three-dimensional matrigel culture over a period of 20 days. In the present study, both cell lines were tested for their suitability to serve as an effect-based in vitro test system for non-genotoxic carcinogens. A software solution for automated Acinus Detection And Morphological Evaluation (ADAME) was developed to automatically acquire acinus images and to determine morphological parameters such as acinus size, lumen size, and acinus roundness. A number of test compounds were tested for their capacity to affect acinus formation and cellular differentiation. Human epidermal growth factor stimulated acinus growth for both cell lines whereas all-trans retinoic acid inhibited acinus growth. The strong estrogen 17β-estradiol had no effect on acinus formation of estrogen receptor (ER)-negative MCF-10A cells, but yielded larger MCF-12A (ER-positive) acini. Thus, the parallel use of both cell lines allows the identification of estrogenic properties of a given test compound.
人乳腺上皮细胞系 MCF-10A 和 MCF-12A 在三维基质胶培养中培养 20 天后，可形成分化良好的类似腺泡的结构。在本研究中，我们测试了这两种细胞系作为非遗传毒性致癌剂的基于效应的体外测试系统的适用性。开发了一种用于自动腺泡检测和形态评估（ADAME）的软件解决方案，以自动获取腺泡图像并确定形态参数，如腺泡大小、腔大小和腺泡圆度。测试了多种测试化合物对腺泡形成和细胞分化的影响。人表皮生长因子刺激两种细胞系的腺泡生长，而全反式视黄酸抑制腺泡生长。强雌激素 17β-雌二醇对雌激素受体（ER）阴性 MCF-10A 细胞的腺泡形成没有影响，但产生了更大的 MCF-12A（ER 阳性）腺泡。因此，两种细胞系的平行使用可以鉴定给定测试化合物的雌激素特性。
