Induction of mesothelioma by intraperitoneal injections of ferric saccharate in male Wistar rats

Our plain-English summary of Induction of mesothelioma by intraperitoneal injections of ferric saccharate in male Wistar rats, by S. Okada, S. Hamazaki, S. Toyokuni, et al (British Journal of Cancer, 1989).

The study

• Authors: S. Okada, S. Hamazaki, S. Toyokuni, O. Midorikawa
• Journal: British Journal of Cancer
• Published: 1989;60(5):708-11
• Cited by: 55 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Iron appears to play a major role in catalysing free radical production, leading to lipid peroxidation and DNA damage. We, therefore, investigated the effect of colloidal iron deposited in the peritoneum. Wistar male rats were given either ferric saccharate, ferric saccharate and nitrilotriacetic acid (NTA), NTA or saline. NTA was shown previously to 'free' iron to promote lipid peroxidation and an iron chelate of NTA is known to be carcinogenic to the kidney. Iron at a dose of 5 mg kg-1 day-1, and saline at a dose of 0.5 ml day-1 were injected i.p. for 3 months. NTA at a dose of 83.5 mg kg-1 day-1 was give i.p. for 5 months. All the rats were killed about a year later for histological examination. In nine of the 19 rats treated with ferric saccharate, mesothelial tumors were induced in the serosa of the tunica vaginalis or the length of the spermatic cord. Among rats treated with ferric saccharate and NTA, seven had localised mesotheliomas in the above locations and six had wide-spread peritoneal mesotheliomas. No mesothelial tumors developed in either NTA treated or saline treated rats. No pleural mesotheliomas were found in any group. These findings add to the evidence that iron is involved in some carcinogenic processes.

In plain English

This was an animal experiment in Japan that tested whether iron deposited in the abdominal lining of rats could cause mesothelioma. It did not test asbestos. Eighty male Wistar rats were randomised into four groups of 20. The groups were given abdominal injections of ferric saccharate (a colloidal iron compound), ferric saccharate plus nitrilotriacetic acid (NTA), NTA alone, or saline, and were killed about a year later. One rat in each iron group died early from injection errors. Of 19 rats given ferric saccharate, 9 developed localised mesothelial tumours on the tunica vaginalis or along the spermatic cord. Of 19 rats given ferric saccharate with NTA, 7 had localised and 6 had widespread peritoneal mesotheliomas. Both iron groups differed significantly from the NTA and saline groups, in which no mesothelial tumours developed. No pleural mesotheliomas were found in any group. The authors concluded that the findings add to evidence that iron is involved in causing some cancers. Their discussion cited other studies suggesting that iron in asbestos may play a role. They noted that their control animals were not given sucrose.

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 (rats randomised into treatment groups, examined by microscope about a year later)
• Who was studied: 80 four-week-old male Slc: Wistar rats from Shizuoka, Japan, in four groups of 20, studied at the Department of Pathology, Kyoto University; 19 'effective' rats in each iron group and 20 in each of the other two groups
• Exposure: Injections into the abdominal cavity (intraperitoneal), 6 days a week. Ferric saccharate, a colloidal iron, was given at 5 mg of iron per kg body weight per day for 3 months to groups 1 and 2. NTA was given at 83.5 mg per kg per day for 5 months to groups 2 and 3. Saline (0.5 ml) was given for 3 months to group 4. No asbestos was used.
• Main results:
  • Ferric saccharate group: 9 of 19 effective rats developed mesothelial tumours, all localised, in the serosa of the tunica vaginalis or along the length of the spermatic cord.
  • Ferric saccharate plus NTA group: of 19 effective rats, 7 had localised mesotheliomas and 6 had wide-spread (diffuse) peritoneal mesotheliomas, 13 in total.
  • No mesothelial tumours developed in the NTA-only group (0 of 20) or the saline group (0 of 20).
  • The ferric saccharate group was significantly different from groups 3 and 4 (P less than 0.002, chi-square test). The ferric saccharate plus NTA group was significantly different from groups 3 and 4 (P less than 0.001, chi-square test).
  • No pleural mesotheliomas were found in any group.
  • Iron was deposited in the peritoneal tissue but was not seen inside the tumour cells.
  • Leydig cell testicular tumours were found in 8 rats of group 1, 9 of group 2, 12 of group 3 and 13 of group 4. One rat in group 1 had a squamous cell carcinoma of the abdominal wall, and one rat in group 2 had leukaemic splenomegaly.
• The authors' conclusion: The authors concluded that the high incidence of mesothelioma caused by colloidal iron adds to evidence that iron is involved in causing some malignant tumours. They believed the effect was mainly due to the iron itself, and that NTA seemed to enhance iron's local cancer-causing action. In their discussion they connected this to other studies suggesting a role for the iron component of asbestos; this study did not test asbestos.
• Limitations the authors state:
  • The authors did not give sucrose to the control animals, although they stated they were not aware of any reports that sucrose causes cancer.
  • The purity of the NTA was not separately analysed.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Peritoneum, Carcinogenic, Tunica Vaginalis, Spermatic Cord, Peritoneal Mesothelioma, Pleural Mesothelioma.

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