- 著者
- Minli WANG Megumi HADA Janice HUFF Janice M. PLUTH Jennifer ANDERSON Peter O'NEILL Francis A. CUCINOTTA
- 出版者
- Journal of Radiation Research Editorial Committee
- 雑誌
- Journal of Radiation Research (ISSN:04493060)
- 巻号頁・発行日
- vol.53, no.1, pp.51-57, 2012 (Released:2012-02-02)
- 参考文献数
- 27
- 被引用文献数
- 13
TGFβ is a key modulator of the Epithelial–Mesenchymal Transition (EMT), a process important in cancer progression and metastasis, which leads to the suppression of epithelial genes and expression of mesenchymal proteins. Ionizing radiation was found to specifically induce expression of the TGF-β1 isoform, which can modulate late post-radiation changes and increase the risk of tumor development and metastasis. Interactions between TGFβ induced EMT and DNA damage responses have not been fully elucidated, particularly at low doses and following different radiation quality exposures. Further characterization of the relationship between radiation quality, EMT and cancer development is warranted. We investigated whether space radiation induced TGFβ dependent EMT, using hTERT immortalized human esophageal epithelial cells (EPC2-hTERT) and non-transformed mink lung epithelial cells (Mv1Lu). We have observed morphologic and molecular alterations in EPC2 and Mv1Lu cells consistent with EMT after pre-treatment with TGFβ1. This effect could be efficiently inhibited in both cell lines by the use of a TGFβRI inhibitor. High-energy silicon or iron nuclei were each able to cause a mild induction of EMT, with the inclusion of TGFβ1 inducing a greatly enhanced EMT phenotype even when cells were irradiated with doses as low as 0.1 Gy. A further enhancement of EMT was achieved at a higher dose of 2 Gy. TGFβRI inhibitor was able to reverse the EMT induced by the combination of TGFβ1 and radiation. These studies indicate that heavy ions, even at a low dose, may trigger the process of TGFβ1–induced EMT, and suggest further studies are needed to determine whether the chronic exposures received in space may potentiate this process in astronauts, leading to an increased risk of cancer.
- 著者
- Megumi HADA Alexandros G. GEORGAKILAS
- 出版者
- Journal of Radiation Research Editorial Committee
- 雑誌
- Journal of Radiation Research (ISSN:04493060)
- 巻号頁・発行日
- vol.49, no.3, pp.203-210, 2008 (Released:2008-05-21)
- 参考文献数
- 79
- 被引用文献数
- 359
Radiation can cause as well as cure cancer. The risk of developing radiation-induced cancer has traditionally been estimated from cancer incidence among survivors of the atomic bombs in Hiroshima and Nagasaki.1) These data provide the best estimate of human cancer risk over the dose range for low linear energy transfer (LET) radiations, such as X- or γ-rays. The situation of estimating the real biological effects becomes even more difficult in the case of high LET particles encountered in space or as the result of domestic exposure to α-particles from radon gas emitters or other radioactive emitters like uranium-238.Complex DNA damage, i.e., the signature of high-LET radiations comprises of closely spaced DNA lesions forming a cluster of DNA damage. The two basic groups of complex DNA damage are double strand breaks (DSBs) and non-DSB oxidative clustered DNA lesions (OCDL). Theoretical analysis and experimental evidence suggest an increased complexity and severity of complex DNA damage with increasing LET (linear energy transfer) and a high mutagenic or carcinogenic potential. Data available on the formation of clustered DNA damage (DSBs and OCDL) by high-LET radiations are often controversial suggesting a variable response to dose and type of radiation. The chemical nature and cellular repair mechanisms of complex DNA damage have been much less characterized than those of isolated DNA lesions like an oxidized base or a single strand break especially in the case of high-LET radiation. This review will focus on the induction of clustered DNA damage by high-LET radiations presenting the earlier and recent relative data.