Abstract
Abstract The relationship between low-dose (<100 mSv) ionizing radiation (LDR) and human cancer risk is controversial. While microenvironment consisting of stromal cells, cytokines and growth factors is modulated by carcinogens to favor carcinogenesis, how LDR impacts this oncogenic process is not well understood. In this study, we investigated the role and mechanism of low-dose ionizing radiation in modulating the response of human lung fibroblasts to carcinogen stimulation and the impacts of which on bronchial epithelial cell transformation. Using a human cytokine antibody array, we found that secretion of proinflammatory cytokines IL-6, CXCL1 and CXCL5 from human lung fibroblasts was induced by cigarette smoke carcinogen benzo[a]pyrene diol epoxide (BPDE), which was inhibited by a low dose of γ-ray irradiation. BPDE induced IL-6 secretion from lung fibroblasts in a dose-dependent manner, which was suppressed when the NF-κB and ERK pathways were blocked. LDR effectively inhibited NF-κB but not ERK activated by BPDE, suggesting that NF-κB is the target for LDR in fibroblasts. In addition, conditioned media from BPDE-treated fibroblasts activated STAT3 in the immortalized human bronchial epithelial cell line Beas-2B, which was blocked with an IL-6 neutralizing antibody as well as by pretreating fibroblasts with LDR. Furthermore, IL-6 significantly enhanced BPDE-induced Beas-2B cell transformation in vitro. These results suggest that LDR inhibits cigarette smoke carcinogen-induced lung carcinogenesis through suppressing secretion of protumorigenic cytokines such as IL-6 from fibroblasts in the tumor-prone microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 393. doi:1538-7445.AM2012-393
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