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Effects of alpha-particle irradiation on cell injury and the expressions of insulin sensitive-related genes in 3T3-L1 preadipocyte

Shao-wei Sun, Yong-zhen Gong, Qin-hui Tuo, Xiao-ying Zhang, Chao ke- Tang, Duan-fang Liao

Exposure of cells to densely ionizing radiation can initiate a series of molecular and cellular events, which result in the gain and loss of functions in critical regulatory genes and cellular damage. In the present study, alpha-particle radiation-induced insulin resistance and toxic injury to 3T3- L1 preadipocyte were observed, and the mechanismunderlying the action was investigated. 3T3-L1 preadipocytes were irradiated by different doses of alpha-particle at 0Gy , 0.3Gy , 0.6Gy , 1.0Gy , 1.5Gy , 2.0Gy , and 4.0Gy . Cloning efficiencywas investigated to evaluate the cellular toxic effect of alpha-particle irradiation on cellular viability. Cytokinesis-block micronucleus technique ( CB-MNT ) and single-cell comet assay COMET assay ÿ were used to observe alpha-particle irradiation-induced DNA damage. Expression of caveolin-1, IRS-1 (insulin receptor substrate-1 ) and GLUT-4 ( glucose transporter-4 ) were analyzed by western blot and Reverse-transcription PCR (RT-PCR).Alpha-particle irradiation inhibited cloning efficiency, and increased micronucleus cells and the DNAdamage in 3T3-L cells in a dose-dependent manner. Alpha-particle irradiation decreased the mRNAexpression of GLUT-4 and IRS-1, and inhibited the protein expression of caveolin-1. The present results indicate that alphaparticle irradiation induced toxic injury and insulin resistance in 3T3-L1 preadipocyte, which might be associated with inhibition of GLUT-4 and IRS-1 expression by down-regulating caveolin-1.