Inhibiting and Enhancing Effects on DNA Repair of Rare Metal Elements in Cultured Human Lymphoblastoid Cells

Abstract

Along with increasing relevance of rare earth (RE) elements in industrial technology, the risk of their environmental release and occupational exposure on human health is of concern. Although many toxicological studies were reported for REs, it is not known how they affect DNA repair. In this study, the effects on DNA repair of all RE ions except radioactive promethium (Pm) were studied. Human lymphoblastoid WTK1cells were irradiated to UV followed by 2h exposure to each RE with and without DNA repair inhibitor cytosine-1β-D- arabinofuranoside (araC), and then single strand breaks (SSBs) were detected by the comet assay. UV-induced pyrimidine dimers are removed by nucleotide excision repair (NER) which consists of recognition of the DNA lesion, excision of a 24–32 nucleotide stretch containing the lesion by dual incision of the damaged DNA strand on both sides, and re-synthesis of the resulting gap by DNA polymerase, and ligation of the nick. SSBs are generated in the incision step of nucleotide excision repair (NER) and disappear in the re-synthesis step of NER. Seven REs, Yb, Lu, Dy, Er, Sc, Pr, and Ce, enhanced comet positive response without araC but not with araC, suggesting that araC is antagonistic to the 7 REs. Since araC inhibits re-synthesis of NER, these seven REs would inhibit the re-synthesis step of NER. Six REs, Tm, Sm, Tb, Gd, Eu, and Y suppressed comet positive responses with and without araC, suggesting that they decreased comet assay detectable SSBs. Therefore, these 6 REs are considered to inhibit the incision step of NER. Only La decreased tail length without araC but increased with araC, suggesting that La increased comet assay detectable SSBs and that only La would enhance the incision step of NER. Neither Nd nor Ho affected tail length with or without araC.