DNA lesions in nuclei isolated from rat tissues following i.p. injection of the carcinogen nickel carbonate were measured by the alkaline elution technique. Kidney, liver, lung, and thymus gland nuclei were examined at 3 and 20 hr after treatment for the presence of DNA single-strand breaks and cross-links. Single-strand breaks were detectable in lung and kidney nuclei, and both DNA-protein and DNA interstrand cross-links were detectable in kidney nuclei. No DNA damage was observed in liver or thymus gland nuclei. A dose response to both single-strand breaks and cross-links was observed in kidney nuclei. Time course studies revealed that maximum DNA damage in kidney nuclei occurred at 2 to 4 hr following injection and also revealed the presence of an active repair process in these nuclei. Repair-resistant DNA-protein cross-links were observed to persist through 48 hr. Tissue and intracellular nickel concentrations as measured by electrothermal atomic absorption spectroscopy were observed to correlate with the levels of DNA damage and repair. A dose response to the concentration of nickel in tissues and nuclei was observed. These results are discussed relative to the solubilization, toxicity, and carcinogenicity of nickel compounds.
This investigation was supported by Grant BC-320 from the American Cancer Society and by an A. P. Sloan Research Fellowship.