Lipoic acid prevents Cr6+ induced cell transformation and the associated genomic dysregulation

Investigation of the transcription profile of cells transformed by Cr6+ in vivo was undertaken. The objective was to elucidate genomic changes underlying the mechanism of action of the carcinogenic dose of Cr6+and their prevention using metabolic antioxidant lipoic acid (LA). Cr6+ was administered intraperitoneally to LPS + TPA challenged Swiss albino mice in host mediated cell transformation assay using peritoneal macrophages in vivo. The cell transforming potential of Cr6+ test doses was validated by gain of anchorage independent growth potential in soft agar and loss of Fc receptor on target cells. LA was administered in equimolar doses. Compared to non-transformed cells, the gene expression profile of transformed cells was found to be dysregulated substantially and in dose dependent manner. Genes showing down regulation were found to be involved in tumour suppression, apoptosis, DNA repair, and cell-cycle. A similar response was noted in the genes pertaining to immune system, morphogenesis, cell-communication, energy-metabolism, and biosynthesis. The co-administration of lipoic acid prevented the transcription dysregulation and cell transformation by Cr6+ in vivo. The influenced pathways seem to be crucial for progression as well as mitigation of Cr toxicity; and their response to LA indicated their critical role in mechanism of anti-carcinogenic action of LA. Results are of importance to mitigate Cr6+ induced occupational cancer hazard.

► Cr6+ induced the cell transformation and dysregulation of relevant genes or pathways in vivo. ► LA prevented toxicity and genomic change run-offs substantially and in dose dependent manner. ► Responsiveness to LA suggested key role of redox reactions in culmination of Cr6+ toxicity. ► Results are of importance for monitoring and mitigation of Cr6+ induced health risk.