HTE (Heterogeneity in Tumor Evolution)
Unraveling Heterogeneity in Tumor Evolution Induced by Diverse Radiation Modes: Insights from Systems Biology.
Carcinogenesis is one of the health risks of space radiation exposures. The occurrence and development of tumors are evolutionary processes driven by genetic and epigenetic mutations. In this study, we employed a comprehensive suite of assays to demonstrate for the first time that long-term low dose-rate exposures to α-particles increase the malignancy of induced tumors rather than the risk of carcinogenesis compared to a single acute exposure with the same total dose. Moreover, we dissected differential malignant mechanisms in tumor evolution induced by the two distinct irradiation modes from systems biology views based on scRNA-seq technology. We found that the former can trigger more copy number variation (CNV) and epithelial-mesenchymal transition (EMT) events, and the activation of DNA damage repair pathways occurred significantly later than with a single acute exposure and involved more specific changes in cellular communication dynamics. In conclusion, our findings provide emerging yet convincing evidence that not only sheds light on why cells exposed to long-term low dose-rate exposures exhibit heightened malignancy, but also offers valuable insights into the genetic determinants driving tumor evolution and heterogeneity.