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DNA lesions were observed in kidney nuclei isolated from rats 20 h after i.p. injection with nickel carbonate. Dose-dependent, nickel-induced DNA crosslinks and DNA single strand breaks were detected using the alkaline elution technique. The DNA crosslinks were determined to be completely DNA-protein in nature. The DNA damage induced by nickel carbonate is discussed relative to the carcinogenicity of nickel compounds.

DNA lesions were detected in rat organ nuclei following an i.p. injection of sodium dichromate. Kidney, liver, and lung nuclei were examined for DNA interstrand cross-links, strand breaks, and DNA-protein cross-links using the alkaline elution technique. The time course for formation of cross-links in kidney nuclei revealed the presence of DNA interstrand and DNA-protein cross-links 1 hr after injection of sodium dichromate. By 40 hr in kidney, DNA interstrand cross-links had been repaired, but DNA-protein cross-links persisted. In liver nuclei, the time course for formation of cross-links after injection of dichromate showed a maximum in DNA-protein cross-linking at 4 hr and a maximum in DNA interstrand cross-linking at 2 hr. By 36 hr, in the liver, both types of lesions had been repaired. In lung nuclei, both DNA interstrand and DNA-protein cross-links were observed 1 hr after dichromate injection; however, by 36 hr, only DNA-protein cross-links persisted. No DNA lesions were detectable in kidney 1 hr after an i.p. injection of chromium(III) chloride. Chromium distribution in rat kidney, liver, and lung was measured and is discussed with respect to the observed DNA lesions. The lung and kidney may be more sensitive than liver to chromium-induced DNA damage, an observation which correlates with the reported toxicity and carcinogenicity data for chromium(VI) in both animals and humans.

DNA cross-links were found in nuclei isolated from the liver and kidney of rats treated with chromate. A dose-dependent relationship between chromate exposure and total DNA cross-links was determined using the alkaline elution technique. DNA cross-links in kidney were mainly DNA-protein in nature. Chromate also induced a small amount of interstrand DNA cross-links in kidney. Liver nuclei contained protein-associated DNA single strand breaks in addition to DNA-protein cross-links. The organotropic DNA damage induced by chromate is discussed in relation to the carcinogenicity and toxicity of chromium(VI) compounds.

DNA damage by chromate in chick embryo hepatocytes has been correlated with the effect of chromate on inducible cell functions. Treatment of chick embryo hepatocytes with chromium(VI) in the form of sodium chromate resulted in the rapid uptake of chromate and the induction of DNA lesions in a time- and concentration-dependent manner. DNA interstrand cross-links, strand breaks and DNA-protein crosslinks, as measured by the alkaline elution technique, were observed after treatment of the hepatocytes with chromate concentrations (2.5- 0 microM) which did not affect cell viability. The effect of chromate on inducible cell functions was measured by assaying propylisopropylacetamide-induced accumulation of porphyrin and glucuronidation of phenol red by intact cells. Chromate inhibited propylisopropylacetamide-induction of porphyrin accumulation and phenol red glucuronidation in a time- and concentration-dependent manner which paralleled DNA damage. DNA damage was removed and inducibility of porphyrin accumulation by propylisopropylacetamide plus deferoxamine methanesulfonate was restored 21 h following a 2 h pretreatment with chromate. Chromium(III) in the form of chromic nitrate at concentrations up to 25 times those used with chromate had no effect on DNA damage or the induction of porphyrin accumulation and phenol red glucuronidation by propylisopropylacetamide in the cultured chick hepatocytes.