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Cancer Biol Ther. 2008 Feb;7(2):208-17. Epub 2007 Nov 3.

Upregulation of stress-response genes with cell cycle arrest induced by carbon ion irradiation in multiple murine tumors models.

Author information

1
RadGenomics Project, National Institute of Radiological Sciences, Inage, Chiba, Japan.

Abstract

OBJECTIVE:

To elucidate the in vivo biological effects induced by carbon-ion irradiation using comprehensive expression analysis.

RESULTS:

In all tumors, the level of expression of several tens of genes, including Ccl3, Ccng1, Cd80, Cdkn1a, Cxcl2, IL7r, Lrdd, Mgmt, Mmp8 and Polk, was significantly altered 6 h and day 1 following C-ion irradiation. At day 3, several hundred genes, many of which are also classified as stress-response or cell-communication genes, including Tnfrsf5, Ikbke and Icam1, were upregulated following C-ion irradiation. The expression level of the majority of these genes was similar following gamma-ray treatment, although the change was not as extensive and intertumor variance was apparent. Several genes, including Ikbke, Serpina3n and Saa3, responded differentially following C-ion irradiation than after gamma-ray irradiation. Pathological investigation and immunohistochemical analysis of Cdkn1a revealed cell cycle arrest with mitotic catastrophe in tumors irradiated by C-ions.

MATERIALS AND METHODS:

We examined gene expression changes after carbon-ion (C-ion) irradiation (290 MeV/m, SOBP 6 cm middle, 50 kev/microm) with a single dose of 30 Gy in four mouse tumors (NR-S1, SCCVII, NFSa and #8520) transplanted into the hind legs of C3H/HeNrs mice, using 44K single-color oligo-microarrays at six hours (h), one day and three days after irradiation. Gamma rays of 30 Gy and 50 Gy were used as a reference beam. Identification of C-ion-responsive genes was based on a false discovery rate of <5% using the Wilcoxon test (p < 0.001) and the Benjamini-Hochberg correction.

CONCLUSIONS:

This study revealed significant C-ion induced upregulation of stress-responsive and cell-communication genes common to different tumor types. These findings provide evidence for the efficacy of this modality for the treatment of local tumors.

PMID:
18073524
[Indexed for MEDLINE]

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