Suzuki Y, Kohyama N
Environ Res. 1984 Oct;35(1):277-92. doi: 10.1016/0013-9351(84)90136-1.
The carcinogenicity of asbestos (amosite and chrysotile) and zeolite (fibrous erionite, mordenite, and synthetic zeolite 4A) were studied in the peritoneum of 586 BALB/C male mice after a single intraperitoneal or intraabdominal wall injection. As controls, 182 mice treated with and without saline solution were used. Both asbestos types and fibrous erionite frequently produced malignant peritoneal tumors after long latency; tumors developed in 93 of 394 animals (23.6%) treated with asbestos or fibrous erionite 7 months or more after administration. All of the induced peritoneal tumors were intimately associated with marked peritoneal fibrosis, in which asbestos or erionite fibers were regularly detected. Histopathologically, 83 (73 fibrous, 9 biphasic, and 1 epithelial) of 93 were consistent with malignant mesotheliomas. Other tumors consisted of 6 plasmacytomas, 1 histiocytoma, 1 liposarcoma, 1 osteosarcoma, and 1 adenocarcinoma of the pancreas. Two of the cases of mesotheliomas were associated with plasmacytoma. In many instances, the primary site of the mesotheliomas seemed to be multiple, the favorite sites being the omentum, mesentery, serosae of the gastrointestinal and genital organs, the diaphragm, the capsule of the liver and spleen, and the abdominal wall peritoneum. In these cases, asbestos or erionite-tissue burden followed by fibrosis was frequently observed. In addition to the 93 peritoneal tumors, 3 extraperitoneal tumors (1 fibrosarcoma and 2 rhabdomyosarcomas) were induced by amosite which was probably accidentally injected into the extraperitoneal connective tissue and the striated muscle tissue of the abdominal wall, respectively. These three tumors were also intimately associated with focal fibrosis in which amosite fibers were detected. Among the three different types of zeolite, only fibrous erionite showed striking carcinogenicity and marked fibrogenicity. The erionite-induced mesotheliomas were similar to those induced by asbestos in exhibiting long latency, in gross appearance, in histology, and in close association with fibrosis. Long-term persistence of asbestos or fibrous erionite around progenitor cells of the induced tumors and the consequent fibrosis seemed to be an important precondition of the malignant transformation of the progenitor cells.
在586只BALB/C雄性小鼠的腹膜内进行单次腹腔或腹壁注射后，研究了石棉（铁石棉和温石棉）和沸石（纤维状毛沸石、丝光沸石和合成沸石4A）的致癌性。作为对照，使用了182只接受和未接受盐溶液处理的小鼠。两种石棉类型和纤维状毛沸石在长时间潜伏期后经常产生恶性腹膜肿瘤；在给药7个月或更长时间后，394只接受石棉或纤维状毛沸石处理 的动物中有93只（23.6%）发生了肿瘤。所有诱导产生的腹膜肿瘤都与明显的腹膜纤维化密切相关，在纤维化组织中经常检测到石棉或毛沸石纤维。组织病理学上，93例中有83例（73例纤维型、9例双相型和1例上皮型）符合恶性间皮瘤。其他肿瘤包括6例浆细胞瘤、1例组织细胞瘤、1例脂肪肉瘤、1例骨肉瘤和1例胰腺腺癌。2例间皮瘤病例与浆细胞瘤有关。在许多情况下，间皮瘤的原发部位似乎是多发的，最常见的部位是大网膜、肠系膜、胃肠道和生殖器官的浆膜、膈肌、肝脾包膜以及腹壁腹膜。在这些病例中，经常观察到石棉或毛沸石组织负荷继之以纤维化。除了93例腹膜肿瘤外，铁石棉还诱导产生了3例腹膜外肿瘤（1例纤维肉瘤和2例横纹肌肉瘤），可能是分别意外注射到腹膜外结缔组织和腹壁横纹肌组织中所致。这三种肿瘤也与检测到铁石棉纤维的局灶性纤维化密切相关。在三种不同类型的沸石中，只有纤维状毛沸石表现出显著的致癌性和明显的致纤维化性。毛沸石诱导的间皮瘤在表现出长时间潜伏期、大体外观、组织学以及与纤维化密切相关方面与石棉诱导的间皮瘤相似。石棉或纤维状毛沸石在诱导肿瘤的祖细胞周围长期存留以及随之而来的纤维化似乎是祖细胞恶性转化的重要前提条件。
