Iron accelerates while magnesium inhibits nickel-induced carcinogenesis in the rat kidney

Abstract

Effects of magnesium basic carbomate (MgCarb) and metallic iron powder (Fe 0) on nickel subsulfide (Ni 3S 2)-induced carcinogenesis were studied in kidneys of male F344/NCR rats. The rats, 20–40/group, received functions of Ni 3S 2 alone (62 μmol Ni or with equimolar doses of MgCarb or Fe 0 into the renal cortex of each pole of the right kidney. Control rats were given MgCarb, Fe 0, or 0.1 ml of 50% aqueous glycerol, the injection vehicle. Final incidence of renal tumors 2 years later the injection of Ni 3S 2 alone or mixed with FE 0 was 60%. However, rats given Ni 3S 2 + Fe 0 developmed renal tumours much more rapidly. In contrast, the incidence of renal tumors in rats given Ni 3S 2 + MgCarb was only 20% ( P < 0.01 vs. Ni 3S 2 alone). No kidney tumors were observed in the control rats. Between weeks 4 and 32 post injection Ni 3S 2 alone caused erythrocytes. This effect was attenuated by Fe 0, but not by MgCarb. Hence, there is no firm correlation between carcinogenecity activity of nikel and its ability to induced erythropoiesis. All kidney tumors were of mesenchymal cell origin and resembled the sarcomatous variant of the classic rat renal mesenchymal tumor. Some of them metastatized to the lungs and other organs. In 3–35 days post-injection , kidneys of rats treated with Ni 3S 2 alone showed moderate to extensive necrosis, inflammation, fibrosis, and degenerative and regenerative proliferative changes in the proximal tubular epithelium at the injection site. Similar, but more severe and multifocal changes were observed in the kidneys of Ni 3S 2 + Fe 0-treated rats. The necrosis was less severe in kidneys injected with Ni 3S 2 + MgCarb, but fibrosis and degenerative and regenerative changes in proximal tubular epithelium were similar to those observed in other treatment groups. Ni 3S 2 deposits were seen inside macropahges and proximal tubular epithelial cells of Ni 3S 2 and Ni 3S 2 + Fe 0-treated kidneys more frequently than in Ni 3S 2 + MgCarb-treated kidneys. Thus, magnesium antagonizes nickel carcinogenesis in the rat kidney while iron tends to enhance it. This result may be related to respectively attenuating or enhancing effects of magnesium and iron on the inflammatory response to Ni 3S 2.