Preliminary Research On Gene Expression In Mouse Bone Marrow Early After High-dose Radiation In Vivo

Aim Radiation can induce changes in gene expression in mammalian cells, and the radiation injury in an organism is also related to the expression changes of many genes. The injury of hematopoietic tissues including bone marrow is one of the major pathological changes of acute radiation syndrome (ARS). To explore the molecular mechanism of bone marrow injury caused by radiation, gene expression of bone marrow in mice after whole body irradiation was studied. Methods The molecular biology technology including suppression subtract!ve hybridization (SSH) and cDNA array hybridization, in addition to the bioinformatics analysis method such as sequence alignment, were used to study differential gene expression of mRNA level in mouse bone marrow early after high dose radiation in vivo. Results Taking cDNA from bone marrow in C57BL/6J mice at 4hr after whole-body irradiation with 7Gy 60 Co -rays as the tester, and the cDNA from the control mice as the driver, the subtracted cDNA library was constructed successfully. After PCR test, 480 clones which have inserted differential cDNA fragments were conserved. The possibly induced genes in bone marrow of C57BL/6J mice at 4hr after whole-body irradiation with 7Gy 60Co y-rays included an unnamed protein, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), neutrophilic granule protein (NPG) ,8100 calcium binding protein A8 (S100a8), Hemoglobin alpha (Hbal), N-methylpurine-DNA glycosylase (MPG), cyclin-dependent kinase inhibitor 1A (CDKN1A), heme oxygenase 1 (HOI) and cytochrome P450, family 2 subfamily e polypeptide 1 (CYP2E1); The possibly repressed genes included chaperonin subunit 3 (CCT3), nucleophosmin 1 (NPM1), N-acetyltransferase 3 (NAT3),prostaglandin-endoperoxide synthase (PTGS1), UDP-glucuronosyltransferase 1 family, member 1 (UGT1A1); Some expressed sequence tags (ESTs) which possibly represented the new radiation-related genes were also separated . CDKN1A and a new EST (BUI01501) were validated to be induced after radiation. Further work need to do to decide whether mRNA level of the other genes were really changed or what was the mechanism of differential gene expression after radiation. Conclusion the biological function and the expression regulation of those differentially expressed genes illuminated that radiation influencedthe hematopoiesis and immune function and the neuroimmunoendocrine network in bone marrow. Some irradiation-induced genes protect organism from genotoxic injury. The work establishes a basis for further research of irradiation-related genes and the molecular mechanism of bone marrow injury caused by radiation.