Study on DNA-protein crosslinks induced by chromate and nickel compounds in vivo with 125I-postlabelling assay.

In an attempt to develop biomarkers of chromate and nickel exposure, we have used a rapid, simple and sensitive 125I-postlabelling assay to detect the formation of DNA-protein crosslinks (DPCs) in different tissues from male Sprague-Dawley rats exposed i.p. to potassium chromate (K2CrO4) and nickel chloride (NiCl2). The results demonstrated that 20 h after rats were injected i.p. with these agents, DPCs were observed in WBC, liver and kidney of rats treated with K2CrO4 in doses ranging from 10 to 40 mg/kg body wt. There was a dose-dependent relationship between chromate exposure and DPCs in WBC and liver, but no DPC increase was shown in lung. In the same way, DPCs were found in WBC and lung of rats treated with NiCl2 in doses ranging from 10 to 30 mg/kg in a dose-dependent manner. The formation of DPCs in different tissues was also observed following repeated exposure of rats to K2CrO4 and NiCl2 (10 mg/kg, i.p.) for 3 weeks. These results were similar with the single dose. It is indicated that chromate and nickel compounds possibly cause DNA or protein damage to form DPCs, suggesting DPCs might be useful as a biomarker for quantitative K2CrO4 and NiCl2 exposure and genotoxic lesions. In addition, WBC were shown to be more sensitive to chromate(VI) and nickel(II) induced DPCs than other targets. There were significant correlations between DPCs induced by K2CrO4 in WBC and liver, and by NiCl2 generated DPCs in WBC and lung, indicating that DPCs in WBC may be a good surrogate for some internal organs of humans exposed to chromate(VI) and nickel(II) compounds.