Particulate hexavalent chromium inhibits global transcription of genes in DNA repair pathways, particularly targeting homologous recombination repair, base excision repair, mismatch repair and microhomology-mediated end-joining.

Hexavalent chromium [Cr(VI)] is a human lung carcinogen with widespread exposure. How Cr(VI) causes cancer is poorly understood, but chromosome instability plays a central role. Inhibition of DNA repair pathways leads to chromosome instability; however, despite the importance of these pathways in the mechanism of Cr(VI)-induced lung carcinogenesis, there are no data considering in-depth analysis on the transcriptional changes of genes involved in them. This study characterized the global transcriptional changes of mRNA expression after Cr(VI) exposure focusing on DNA repair pathways. The repair pathways considered included homologous recombination repair, non-homologous end joining, microhomology-directed end-joining, single strand annealing, mismatch repair, base excision repair, nucleotide excision repair and crosslink repair. Normal human lung fibroblast cells were exposed to increasing zinc chromate concentrations for 24, 72 or 120 h then RNA was extracted and sequenced. Our results indicate Cr(VI) causes differential expression of genes in lung cancer pathways and downregulates expression of some genes in all 8 DNA repair pathways. Homologous recombination repair, mismatch repair, base excision repair and microhomology-directed end-joining were the most affected pathways. This study provides a critical in-depth analysis of the effects of Cr(VI) on DNA repair pathways and contributes new insights into the mechanism of Cr(VI)-carcinogenesis.