Craighead J E, Akley N J, Gould L B, Libbus B L
Department of Pathology, College of Medicine, University of Vermont, Burlington 05405.
Am J Pathol. 1987 Dec;129(3):448-62.
Mesotheliomas developed in rats in the abdominal cavity 6-23 months after peritoneal introduction of chrysotile and crocidolite asbestos. The tumors were strikingly similar to those occurring in man both with regard to histologic features and growth patterns. The authors have cultured cells from these tumors and established epithelial lines with a variety of karyologic features and doubling times shorter than those of normal mesothelial cells. Lines of diploid or near-diploid tumor cells required serum in the medium to replicate, whereas most aneuploid cell lines were maintained in a serum-free medium. In serum-free medium, the aneuploid line monolayers produced anchorage-independent excrescent masses of cells which "bud" and float free. These spheroids, which strikingly resemble the papillary structures in human mesotheliomas, are composed of mesothelial-like cells that produce hyaluronic acid and have a rich complement of intermediate filaments, predominantly cytokeratins. Aneuploid cells also replicated in soft agar with high efficiency, whereas the diploid and near-diploid cells did not. All but one cultured cell line, regardless of karyotype, produced tumors after subcutaneous or intraperitoneal inoculation (or both). Aneuploid cells caused lung tumors sporadically when introduced intravenously. Comparative analysis of the nuclear DNA of primary tumors and cultured cells demonstrated a high degree of chromosomal instability and selection among cells during early passage in vitro.
在腹腔内注入温石棉和青石棉后6 - 23个月，大鼠发生了间皮瘤。这些肿瘤在组织学特征和生长模式方面与人类发生的肿瘤极为相似。作者从这些肿瘤中培养细胞，并建立了具有多种核型特征且倍增时间比正常间皮细胞短的上皮细胞系。二倍体或近二倍体肿瘤细胞系在培养基中需要血清才能复制，而大多数非整倍体细胞系可在无血清培养基中维持生长。在无血清培养基中，非整倍体细胞系单层产生不依赖贴壁的细胞团块，这些细胞团块“出芽”并游离漂浮。这些球体与人类间皮瘤中的乳头状结构极为相似，由产生透明质酸且富含中间丝（主要是细胞角蛋白）的间皮样细胞组成。非整倍体细胞在软琼脂中也能高效复制，而二倍体和近二倍体细胞则不能。除一个培养细胞系外，所有细胞系无论核型如何，在皮下或腹腔内接种（或两者皆接种）后都会产生肿瘤。非整倍体细胞静脉注射时偶尔会引发肺部肿瘤。对原发性肿瘤和培养细胞的核DNA进行比较分析表明，在体外早期传代过程中细胞存在高度的染色体不稳定性和细胞选择。
