Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis

Our plain-English summary of Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis, by D. Aierken, Y. Okazaki, S.H. Chew, et al (Nagoya Journal of Medical Science, 2014).

The study

• Authors: D. Aierken, Y. Okazaki, S.H. Chew, A. Sakai, Y. Wang, H. Nagai, N. Misawa, N. Kohyama, S. Toyokuni
• Journal: Nagoya Journal of Medical Science
• Published: 2014;76(1-2):149-60
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Asbestos was abundantly used in industry during the last century. Currently, asbestos confers a heavy social burden due to an increasing number of patients with malignant mesothelioma (MM), which develops after a long incubation period. Many studies have been conducted on the effects of the asbestos types that were most commonly used for commercial applications. However, there are few studies describing the effects of the less common types, or minor asbestos. We performed a rat carcinogenesis study using Japanese tremolite and Afghan anthophyllite. Whereas more than 50% of tremolite fibers had a diameter of < 500 nm, only a small fraction of anthophyllite fibers had a diameter of < 500 nm. We intraperitoneally injected 1 or 10 mg of asbestos into F1 Fischer-344/Brown-Norway rats. In half of the animals, repeated intraperitoneal injections of nitrilotriacetate (NTA), an iron chelator to promote Fenton reaction, were performed to evaluate the potential involvement of iron overload. Tremolite induced MM with a high incidence (96% with 10 mg; 52% with 1 mg), and males were more susceptible than females. Histology was confirmed using immunohistochemistry, and most MMs were characterized as the sarcomatoid or biphasic subtype. Unexpectedly NTA showed an inhibitory effect in females. In contrast, anthophyllite induced no MM after an observation period of 550 days. The results suggest that the carcinogenicity of anthophyllite is weaker than formerly reported, whereas that of tremolite is as potent as major asbestos as compared with our previous data.

In plain English

This animal experiment tested Japanese tremolite and Afghan anthophyllite, two less common asbestos types, in 270 hybrid rats. Rats received a total of 1 or 10 mg of one fiber type, in two abdominal injections. Half also received weekly injections of nitrilotriacetate (NTA), an iron chelator, for 12 weeks. Controls got NTA or saline. Rats were observed for 550 days. Over half of tremolite fibers were thinner than 500 nm; most anthophyllite fibers were thicker than 1000 nm. Tremolite caused peritoneal mesothelioma in 96.1% of rats given 10 mg and 51.9% given 1 mg. The article's subgroup counts add up to 49 of 51 and 28 of 54 (three males died during injections). At 1 mg, males were more susceptible than females. NTA significantly delayed deaths only in females given 10 mg tremolite. No anthophyllite-treated rat developed mesothelioma. The authors concluded that this tremolite was potently carcinogenic to mesothelial cells and this anthophyllite preparation was not. They noted the fibers were not standardized and more finely ground anthophyllite could not be ruled out as carcinogenic. They noted abdominal injection differs from human exposure.

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 carcinogenesis experiment (intraperitoneal injection in rats)
• Who was studied: 270 six-week-old F1 Fischer-344 × Brown-Norway hybrid rats (150 female, 120 male). Each of the 4 asbestos groups had 54 animals (24 males, 30 females). The rest were controls given NTA or saline. Rats were followed for 550 days.
• Exposure: Japanese tremolite (Yamaga City, Kumamoto; short fiber preparation) or Afghan anthophyllite. Each was given as two intraperitoneal injections of 0.5 or 5 mg a week apart, for a total of 1 or 10 mg per rat. Half of each group also received NTA at 80 mg/kg once a week for 12 weeks.
• Main results:
  • Fiber shape: more than 50% of tremolite fibers were under 500 nm in diameter, while most anthophyllite fibers were over 1000 nm.
  • Fiber length: about 15% of tremolite fibers and 100% of anthophyllite fibers were longer than 20 μm.
  • 10 mg tremolite: 96.1% of rats developed mesothelioma within 550 days (male NTA 10/10; male saline 11/11; female NTA 13/15; female saline 15/15). These subgroup counts add up to 49 of 51 rats. Three males died during the injection period and are not in these counts.
  • 1 mg tremolite: 51.9% of rats developed mesothelioma within 550 days (male NTA 11/12; male saline 9/12; female NTA 5/15; female saline 3/15). These subgroup counts add up to 28 of 54 rats.
  • In the 1 mg tremolite groups, males were more susceptible than females (NTA P=0.0031; saline P=0.0007; combined P less than 0.0001, log-rank test).
  • NTA significantly delayed deaths only in the female 10 mg tremolite group (P=0.0072). In all other groups, NTA had no significant effects.
  • No rat injected with anthophyllite developed mesothelioma.
  • The sarcomatoid subtype was the most common in the tremolite-induced tumors.
  • Heavy iron deposits were seen in most tremolite-injected rats, and much less in anthophyllite-injected rats.
• The authors' conclusion: The authors concluded that the short-fiber tremolite preparation was potently carcinogenic to mesothelial cells, while the Afghan anthophyllite preparation was not. They also concluded that fiber diameter appears more important than fiber length for mesothelial carcinogenesis.
• Limitations the authors state:
  • The minor asbestos fibers used were not standardized like the UICC major asbestos samples.
  • The authors could not rule out that more finely ground anthophyllite is carcinogenic.
  • Intraperitoneal injection gives maximum exposure to mesothelial cells and is not the same as human exposure.
  • The anthophyllite result conflicts with earlier rat studies. The authors said this may be due to different fibers, a different rat strain, or both, and that strain differences need further study.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Anthophyllite, Lung cancer, Mesothelioma, Tremolite.

Medical terms in this study, explained in our Lexicon: Tremolite, Anthophyllite, Carcinogenesis, Malignant Mesothelioma, Fenton Reaction, Histology, Immunohistochemistry, Sarcomatoid.

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