Summary 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-' day-', and saline at a dose of 0.5 ml day-' were injected i.p. for 3 months. NTA at a dose of 83.5 mg kg-' day-' 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.

The deleterious effects of aluminum(AL) and iron(Fe) on bone formation were studied in the presence of nitrilotriacetate (NTA) as a chelator. Both Al-NTA (1.0-1.5 mg Al/kg/day, n = 12)- and ferric nitrilotriacetate (Fe-NTA) (2.0 mg/kg/day, n = 4)-treated Wistar rats showed renal insufficiency blood urea nitrogen [BUN] levels of 25 +/- 8.8-20 +/- 0.7 compared to 12 +/- 0.7-11 +/- 0.4 mg/dl), osteomalacia with a relative osteoid volume of 31.5 +/- 5.6-13.2 +/- 2.4 compared to 4.6 +/- 1.8-0.83 +/- 0.12%, and bone growth retardation (3.1 +/- 0-3.0 +/- 0.2 compared to 3.4 +/- 0-3.3 +/- 0.1 cm) in 24 control rats. Dietary vitamin E(VE) supplementation prevented the Fe-NTA-induced impairment, but not the Al-NTA toxicity. Aluminum was deposited at the interface between osteoid and mineralized bone, while Fe was deposited in the osteoblasts and osteoclasts. There seems to be a positive correlation between hypophosphatemia and osteomalacia but carboxy-terminal parathyroid hormone (C-PTH) and calcium (Ca) levels in the serum were not related to the degree of osteomalacia. Administration of Al-NTA results in more bone Al deposition than that of aluminum chloride (AlCl3) (450 +/- 40 compared to 211 +/- 18 mg/kg fat-free dry weight). The Fe-NTA bone change is related to VE-preventable cellular injury, being consistent with the notion that Fe-NTA toxicity is caused by lipid peroxidation. Al-NTA can be used as an animal model of renal osteodystrophy. Osteodystrophy by Al in chronic renal failure may be mediated by the intrinsic chelator or chelating substance(s) retained in the body fluid due to renal insufficiency.

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