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

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• 作者：Sushil Kumar^a ; ^{sushilkumar@iitr.res.in} ; ^{sushilkumar.iitr@gmail.com} ; Akanksha Nigam^a ; Shivam Priya^a ; Preeti Bajpai^b ; Roli Budhwar^a
• 关键词：Cr6+ ; Hexavalent chromium ; ROS ; Reactive oxygen species ; K2Cr2O7 ; Potassium dichromate ; EDTA ; Ethylene-diamine tetra acetic acid ; DEPC ; Diethylpyrocarbonate ; GM-CSF ; Granulocyte-macrophage colony stimulating factor ; TPA ; 12-o-Tetradecanoyl-phorbol 13-acet
• 刊名：Environmental Toxicology and Pharmacology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：36
• 期：1
• 页码：182-193
• 全文大小：1463 K

文摘

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.