Schaeffer W I, Heintz N H
In Vitro. 1978 May;14(5):418-27. doi: 10.1007/BF02616103.
Chronic exposure of a cloned rat hepatocyte culture (RL-PR-C) to a subtoxic, sublethal dose of aflatoxin B1 resulted in malignant transformation. Continuous exposure to aflatoxin B1 caused increasing tumorigenic potential as tested by back injection into isogenic animals. Control cultures exhibited spontaneous transformation, although approximately 20 passages beyond the chemically induced event. Neither aflatoxin-treated nor control cultures exhibited cytopathological morphology, formation of cell foci, growth in soft agar, or irregular fibroblast-like growth patterns that could be specifically related to the onset of tumorigenic potential. In general, those parameters commonly used to monitor fibroblast cultures for transformation in vitro were not applicable for assessing the tumorigenic potential of these epithelial cells. Karyotypic analyses revealed no specific chromosomal aberrations associated with aflatoxin treatment; however, chromosomal instability was a property of the tumorigenic cell populations. Injection of both aflatoxin-treated and control cultures at passage 56 resulted in tumors indicative of both carcinoma and sarcoma indicating to us the multipotency of these epithelial cells transformed in vitro.
将克隆的大鼠肝细胞培养物（RL-PR-C）长期暴露于亚毒性、亚致死剂量的黄曲霉毒素B1会导致恶性转化。通过回注到同基因动物体内进行测试，持续暴露于黄曲霉毒素B1会导致致瘤潜力增加。对照培养物表现出自发转化，尽管比化学诱导事件晚约20代。黄曲霉毒素处理组和对照组培养物均未表现出细胞病理形态、细胞集落形成、软琼脂中生长或与致瘤潜力开始相关的不规则成纤维细胞样生长模式。一般来说，那些常用于监测成纤维细胞培养物体外转化的参数不适用于评估这些上皮细胞的致瘤潜力。核型分析显示，与黄曲霉毒素处理无关的特定染色体畸变；然而，染色体不稳定性是致瘤细胞群体的一个特性。在第56代时注射黄曲霉毒素处理组和对照组培养物均导致了指示癌和肉瘤的肿瘤，这向我们表明了这些体外转化的上皮细胞具有多能性。
