Survival genes expression analysis following ionizing radiation to LiCl treated KG1a cells

Abstract

Purpose: Lithium chloride (LiCl) is clinically used for manic disorders. Its role has been shown in improving cell survival by decreasing Bax and p53 expression and increasing Bcl-2 concentration in the cell. This potential of LiCl is responsible for reducing irradiated cell death. In this study, we have explored the role of LiCl as a radioprotectant affecting survival genes.

Materials and methods: To find out the cellular response upon LiCl pretreatment to radiation-exposed KG1a cells; viability, clonogenic assay and microarray studies were performed. This was followed by the detection of transcription factor binding motif in coregulated genes. These results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and chromatin immunoprecipitation (CHIP).

Results: LiCl improved irradiated KG1a cell survival and its clonogenicity at 2 mM concentration (clinically used). Microarray data analysis showed differential expression of cell-protecting genes playing an important role in apoptosis, cell cycle, adhesion and inflammation, etc. The coregulation analysis revealed genes involved in bile acid biosynthesis were also affected by LiCl treatment, these genes are likely to be responsible for radiation-induced gastrointestinal (GI) syndrome through bile production.

Conclusions: This is the first study with respect to global genetic expression upon LiCl treatment to radiation-exposed cells. Our results suggest considering repurposing of LiCl as a protective agent for radiation injury.

Keywords:

• Microarray data analysis
• cell survival
• clustering
• coregulated expression
• network analysis
• bile acid synthesis

Acknowledgments

Authors acknowledge Mr. Rakesh Pandey for performing comet assay and analysis of comets. Authors also show gratitude toward Dr. A.N. Bhatt for providing critical comments on the manuscript. We thank Director, INMAS, for his continuous support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was funded by Defence Research Development Organisation (DRDO), India, project no. ST/P1/2008/INM/311/1.6.

Notes on contributors

Yogesh Kumar Verma

Dr. Yogesh Kumar Verma, MNABS, is working as Scientist ‘D’ in INMAS, DRDO, Delhi. He completed his M.Sc. and Ph.D. in Biomedical Science from Delhi University. He also has another M.Sc. degree in Bioinformatics from Punjab Technical University. In the year 2009, he joined INMAS, DRDO, Delhi, as Scienitst ‘C’. He is presently working in the area of stem cell research, microencapsulation, tissue engineering and omics data mining and analysis for repairing/regenerating various types of tissues for Defense application.

Ajay Kumar Singh

Dr. Ajay Kumar Singh, Distinguished Scientist (DS)/Scientist ‘H’ presently holding the charge of Director General Life Sciences, DRDO Headquarters, Delhi, India. Dr. A.K. Singh completed his M.Sc (Hons.) in Biophysics from Punjab University, Chandigarh, and obtained his doctorate from Jamia Milia Islamia (JMI) University, Delhi, on Infection Imaging.

Gangenahalli Ugraiah Gurudutta

Dr. Gurudutta Gangenahalli, FICS, FNA Biol Sci’s, FICI (Ire), FRAM (Ire), FRSC (UK), FRSB (UK), FRSM (UK), presently an Additional Director & Founding Head of the Division of Stem Cell Research at INMAS, DRDO, Delhi, India. He is spearheading the group and focuses on the work involving understanding of human stem cell fate response signaling for therapeutic purpose. This work constitutes the basis to facilitate the fate modifications strategies, by microencapsulation, tissue-engineering, computational analysis of genome data, data mining, and to develop new and effective fate modifying molecules which enhance stem cell regenerative potentials bringing their effective applications closer to bench-to-bedside, particularly for injury treatment of Defence interest.