Malignant mesothelioma induced by asbestos and zeolite in the mouse peritoneal cavity

Our plain-English summary of Malignant mesothelioma induced by asbestos and zeolite in the mouse peritoneal cavity, by Y. Suzuki, N. Kohyama (Environmental Research, 1984).

The study

• Authors: Y. Suzuki, N. Kohyama
• Journal: Environmental Research
• Published: 1984;35(1):277-92
• Cited by: 83 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

In this animal experiment, 768 male BALB/C mice were studied: 291 received asbestos (amosite or chrysotile), 295 received zeolite minerals (fibrous erionite, mordenite or synthetic zeolite 4A) and 182 were controls. Most treated mice got one injection into the abdominal cavity, at doses from 0.5 to 20 mg, and were examined after death up to 23 months later. No peritoneal tumors appeared before 7 months. Before then, 192 of 586 treated mice died or became very sick, mostly from peritoneal fibrosis followed by intestinal obstruction. From 7 to 23 months, peritoneal tumors developed in 39 of 192 (20.3%) asbestos-treated mice and 54 of 112 (48.2%) fibrous erionite-treated mice. Of 93 peritoneal tumors, 83 were malignant mesotheliomas, mostly of the fibrous type. Mordenite, synthetic zeolite 4A, the controls and the 2 mg UICC chrysotile group produced no tumors. All tumors were closely associated with fibrosis. The authors concluded that fibrous erionite, like asbestos, is clearly carcinogenic in animals. They cautioned that animal findings may not apply directly to human mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal experiment: a single injection of mineral fibers into the peritoneal cavity of mice, with long-term observation and necropsy
• Who was studied: 768 male BALB/C mice, aged 5 to 6 weeks when exposed: 291 asbestos-treated, 295 zeolite-treated and 182 controls (saline-treated or untreated), all necropsied when sacrificed or found dead between 0 and 23 months after injection
• Exposure: UICC amosite, UICC chrysotile B and Calidria chrysotile (asbestos), and two samples of fibrous erionite (Erionite I and II), mordenite and synthetic zeolite 4A (zeolites), given in doses of 0.5, 2, 10 or 20 mg in 1 ml saline. Most mice received a single intraperitoneal injection. Group 7 received both 2 mg chrysotile and 2 mg amosite. Group 8 received 10 mg amosite into the abdominal wall.
• Main results:
  • No peritoneal tumors were found in any group before 7 months after exposure
  • Before 7 months, 192 of 586 treated mice were found dead or very sick, most commonly from peritoneal fibrosis followed by intestinal obstruction
  • Between 7 and 23 months, peritoneal tumors (mainly malignant mesothelioma) occurred in 39 of 192 (20.3%) asbestos-treated mice and 54 of 112 (48.2%) fibrous erionite-treated mice
  • Tumor incidence by group ranged from 60% in the double-treated group (2 mg UICC chrysotile plus 2 mg amosite, Group 7) to 18.2% in the UICC chrysotile 20 mg group (Group 4)
  • No peritoneal tumors developed in the UICC chrysotile 2 mg group, the abdominal-wall amosite 10 mg group, the mordenite group, the synthetic zeolite 4A group, or the saline and untreated control groups
  • The 93 peritoneal tumors were 83 malignant mesotheliomas, 6 plasmacytomas, 1 histiocytoma, 1 liposarcoma, 1 extraskeletal osteosarcoma and 1 adenocarcinoma of the pancreas
  • Of the 83 malignant mesotheliomas, 73 were fibrous, 9 biphasic and 1 epithelial
  • Three tumors outside the peritoneum were attributed to amosite: one subcutaneous fibrosarcoma in the amosite 20 mg group and two rhabdomyosarcomas in the abdominal-wall amosite group
  • All tumors induced by asbestos and fibrous erionite were closely associated with fibrosis
• The authors' conclusion: The authors concluded that, like asbestos, fibrous erionite is clearly carcinogenic and induced malignant mesothelioma at a high rate in animals. They also stated that mordenite and synthetic zeolite 4A did not induce peritoneal tumors.
• Limitations the authors state:
  • The authors stated that mechanisms suggested by animal experiments may not apply directly to human mesothelioma, for example because mice live about 2 years
  • Larger doses and artificial exposure by injection had to be used to induce mesothelioma in animals
  • It is not known whether the short, thin fibers that made up most of the samples or the minority of long, thin fibers were responsible for the tumors
  • The authors did not themselves characterize the Calidria chrysotile sample

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Santa Rita mine, Joaquin Ridge near Coalinga, California

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Chrysotile, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Zeolite, Peritoneal Cavity, Amosite, Chrysotile, erionite, Peritoneum, Latency.

Related studies

• CT findings in malignant pleural mesothelioma related to nonoccupational exposure to asbestos and fibrous zeolite (erionite) — C. Erzen, M. Eryilmaz, et al. (1991)
• Analysis of the biological and chemical reactivity of zeolite-based aluminosilicate fibers and particulates — E. Fach, W.J. Waldman, et al. (2002)
• Natural fibrous zeolites and their carcinogenicity-a review — K.R. Spurny (1983)
• Prospective clinical and radiologic study of zeolite-exposed Turkish immigrants in Sweden — M. Ozesmi, G. Hillerdal, et al. (1990)
• Phenotypic characterisation of peripheral blood lymphoid cells in people exposed to fibrous zeolite — M. Ozesmi, A. Karlsson-Parra, et al. (1986)
• Antitumor-specific T-cell responses induced by oncolytic adenovirus ONCOS-102 (AdV5/3-D24-GM-CSF) in peritoneal mesothelioma mouse model — L. Kuryk, A.W. Møller, et al. (2018)

Browse more research in Environmental Research, or return to medical research.