Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detection

Aluminum (Al) is extensively used for making cooking utensils and its presence in the aquatic environment may occur through acid mine drainage and wastewater discharge. Al is known to induce genotoxicity in human cells, rodents, and fish. Nucleotide excision repair (NER) eliminates helix-twisting DNA lesions such as UV-induced dipyrimidine photoproducts. Because our earlier investigation revealed the operation of NER in zebrafish (Danio rerio) embryos, this study explored if inhibition of NER could be a mechanism of Al-induced genotoxicity using zebrafish embryo as a model system. An acute fish embryo toxicity test indicated that Al (as aluminum sulfate) at 2-15 mg/L were nonlethal to zebrafish embryos, yet exposure of embryos at 1 h post fertilization (hpf) to Al at 10-15 mg/L for 71 h significantly repressed their NER capacity monitored by a transcription-based DNA repair assay. Band shift analysis indicated a higher sensitivity of (6-4) photoproduct (6-4PP) than cyclobutane pyrimidine dimer (CPD) detecting activities to Al, reflecting the preferential influence of Al on the detection of strongly distorted DNA lesions. Time-course experiments showed a delayed response of NER to Al as repair machinery was unaffected by Al at 15 mg/L following a 35-h exposure, while Al treatment for the same period obviously inhibited 6-4PP binding activities although the gene expression of damage recognition factors remained active. Inhibition of 6-4PP detection blocked downstream lesion incision/excision detected by a ter-minal deoxy transferase-mediated end labeling assay. As the disturbance of damage sensing preceded that of the overall repair process, Al exposure was believed to downregulate NER capacity by inhibiting the activities of lesion detection proteins. Our results revealed the ability of Al to enhance its genotoxicity by suppressing NER capacity.

Automated summary

This study investigated the effects of aluminum on DNA damage repair using zebrafish embryos as a model system. The results showed that aluminum enhances its genotoxicity by inhibiting the nucleotide excision repair (NER) capacity.