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Malignant mesothelioma induced by asbestos and zeolite in the mouse peritoneal cavity
Abstract:
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.
Insights
Asbestos and fibrous erionite cause malignant peritoneal tumors and fibrosis in mice. These fibers, persisting long-term, are linked to cancer development, highlighting their carcinogenicity.
Area of Science:
- Toxicology
- Oncology
- Materials Science
Background:
- Asbestos and certain zeolites are known environmental and occupational hazards.
- Understanding the carcinogenicity of these mineral fibers is crucial for public health.
- Previous studies have indicated potential links between fibrous minerals and cancer.
Purpose of the Study:
- To investigate the carcinogenicity of amosite, chrysotile asbestos, and fibrous erionite, mordenite, and synthetic zeolite 4A.
- To evaluate the role of these materials in inducing peritoneal tumors and fibrosis in a mouse model.
- To compare the carcinogenic potential of asbestos and fibrous erionite.
Main Methods:
- BALB/C male mice (n=768) received single intraperitoneal or intraabdominal wall injections.
- Groups were treated with amosite, chrysotile, fibrous erionite, mordenite, synthetic zeolite 4A, or saline (control).
- Tumor development, latency, histology, and association with fibrosis were assessed over time.
Main Results:
- Asbestos (amosite, chrysotile) and fibrous erionite induced malignant peritoneal tumors (23.6% incidence) with long latency.
- All induced tumors were associated with marked peritoneal fibrosis, containing detected fibers.
- Fibrous erionite demonstrated striking carcinogenicity and fibrogenicity, similar to asbestos.
Conclusions:
- Long-term persistence of asbestos or fibrous erionite fibers, coupled with fibrosis, is a key factor in malignant transformation.
- Fibrous erionite is a potent carcinogen, comparable to asbestos, inducing mesotheliomas.
- These findings underscore the significant health risks associated with exposure to these specific mineral fibers.