Enhancement by asbestos of oncogenesis by Moloney murine sarcoma virus in CBA mice

Our plain-English summary of Enhancement by asbestos of oncogenesis by Moloney murine sarcoma virus in CBA mice, by K. Kanazawa, T. Yamamoto, Y. Yuasa (International Journal of Cancer, 1979).

The study

• Authors: K. Kanazawa, T. Yamamoto, Y. Yuasa
• Journal: International Journal of Cancer
• Published: 1979;23(6):866-74
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Five micrograms of finely ground crocidolite asbestos (UICC standard sample) were injected intraperitoneally into 3-week-old CBA mice, together with 10(5) FFU of Moloney murine sarcoma virus. Altogether 44 out of 61 mice (72.1%) so treated developed palpable intraperitoneal tumours, and half of these died of such tumours within 100 days. The same amount of quartz and carbon similarly administered gave lower tumour incidences, namely, 19.4% (3.2% fatal) and 11.9% (1.5% fatal) respectively. Only 1 out of 59 mice inoculated with the virus alone developed a palpable intraperitoneal tumour, and this regressed spontaneously within 10 days of its first appearance. No tumours were encountered in mice treated with either asbestos, quartz or carbon alone. All the neoplasms had the appearance, under the light microscope, of anaplastic sarcomas. Most of them were confined to the serosal surface of the abdominal cavity, although invasion of underlying tissues was observed in some of the animals that died. Electron microscopical examination of tumours revealed the presence of C-type particles budding off from cellular surface. Some neoplastic cells showed characteristic features of mesothelial lining cells. The role of milky spots (taches laiteuses) in oncogenesis by asbestos and virus, especially in the induction of mesothelioma, is discussed.

In plain English

In this animal experiment, the authors injected 3-week-old CBA mice in the abdomen with 5 micrograms of finely ground crocidolite asbestos, quartz or carbon powder. Each was given alone or mixed with Moloney murine sarcoma virus, a tumour-causing mouse virus; other mice got the virus alone or saline only. Within 100 days, 44 of 61 mice given virus plus crocidolite (72.1%) developed tumours that could be felt, and 22 (36.1%) died of them. With virus plus quartz, 12 of 62 mice (19.4%) developed tumours and two died. With virus plus carbon, 8 mice developed tumours and one died. The text gives this as 8 of 67 (11.9%), though the tables list 61 mice in this group. One of 59 mice given virus alone developed a tumour, which regressed within 10 days. No tumours appeared in mice given asbestos, quartz, carbon or saline alone. The tumours looked like anaplastic sarcomas. Some tumour cells resembled mesothelial cells, but the authors said further study was needed before any could be called mesotheliomas. The authors concluded that asbestos acted as a co-carcinogen or modulator of tumour formation by the virus.

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: mice randomly allocated by litter to eight groups given intraperitoneal injections of virus, particles, both, or saline, and followed for tumours for 100 days
• Who was studied: 3-week-old CBA mice bred at the Institute of Medical Science, University of Tokyo, Japan. There were eight groups: seven of about 60 mice each and a saline-only control group of 98 mice from 12 litters.
• Exposure: A single intraperitoneal injection of 5 micrograms of finely ground UICC standard crocidolite asbestos, quartz, or carbon (charcoal) powder, each given alone or mixed with 10^5 focus-forming units of Moloney murine sarcoma virus. Controls received the virus alone or saline only.
• Main results:
  • Virus plus crocidolite group: 21 of 61 mice (34.4%) had palpable tumours within 10 days, and 44 of 61 (72.1%) within 100 days
  • Virus plus crocidolite group: in 22 mice (36.1%) the tumours grew and caused death within 100 days
  • Virus plus quartz group: 12 of 62 mice (19.4%) developed palpable tumours, and 2 of them (3.2% of the group) died of intraperitoneal sarcomas within 100 days
  • Virus plus carbon group: 8 mice developed palpable tumours and one died. The text gives the denominator as 67 (11.9%), but Tables I and II list 61 mice in this group.
  • Virus alone: 1 of 59 mice (1.7%) developed a palpable tumour, which regressed spontaneously within 10 days
  • No palpable or lethal tumours occurred in mice given saline, crocidolite, quartz or carbon alone
  • Death from tumour before 100 days was not statistically significantly increased with virus plus quartz or virus plus carbon compared with virus alone
  • Asbestos fibres were never found in tumour tissue itself, only occasionally among macrophages surrounded by tumour cells
  • Electron microscopy showed C-type virus particles budding from tumour cells
• The authors' conclusion: The authors concluded that in this experiment asbestos acted as a co-carcinogen or modulator in tumour formation by the virus in the mesothelium. They also suggested that milky spots on the serous surfaces may be where such tumours start.
• Limitations the authors state:
  • The authors said the tumours could not be positively identified as mesotheliomas without further study
  • Tissue patterns typical of some diffuse forms of human malignant mesothelioma were not seen
  • The authors report that in a later study, 4-week-old mice of the same strain given the same treatment were resistant during 100 days, so the result depended on the age of the mice

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Oncogenesis, Sarcoma, Crocidolite, UICC, Neoplasm, Serosal Surface, Mesothelioma.

Related studies

• Tumorigenicity of cellulose fibers injected into the rat peritoneal cavity — R.T. Cullen, B.G. Miller, et al. (2002)
• The in vitro cytotoxicity of asbestos fibers: I. P388D1 cells — A. Wright, H. Cowie, et al. (1986)
• Milky spots (Taches laiteuses) as structures which trap asbestos in mesothelial layers and their significance in the pathogenesis of mesothelial neoplasia — K. Kanazawa, F.J. Roe, et al. (1979)
• Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages — D.J. Blake, S.A. Wetzel, et al. (2008)
• Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice — A. Takagi, A. Hirose, et al. (2012)
• Establishment of a murine model of malignant mesothelioma — M.R. Davis, L.S. Manning, et al. (1992)

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