title: Lipoic acid prevents Cr(6+) induced cell transformation and the associated genomic dysregulation.
abstract: Investigation of the transcription profile of cells transformed by Cr(6+) in vivo was undertaken. The objective was to elucidate genomic changes underlying the mechanism of action of the carcinogenic dose of Cr(6+)and their prevention using metabolic antioxidant lipoic acid (LA). Cr(6+) 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 Cr(6+) 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 Cr(6+) 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 Cr(6+) induced occupational cancer hazard.
authors.affiliation: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P Box 80, Lucknow, India. sushilkumar@iitr.res.in
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
authors.forename: Akanksha
authors.initials: A
authors.lastname: Nigam
authors.forename: Shivam
authors.initials: S
authors.lastname: Priya
authors.forename: Preeti
authors.initials: P
authors.lastname: Bajpai
authors.forename: Roli
authors.initials: R
authors.lastname: Budhwar
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002857:Chromium / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D046228:Microarray Analysis; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D002857:Chromium; C074702:chromium hexavalent ion; D008063:Thioctic Acid