DNA damage responses in cancer stem cells: Implications for cancer therapeutic strategies

The identification of cancer stem cells(CSCs) that are responsible for tumor initiation, growth, metastasis, and therapeutic resistance might lead to a new thinking on cancer treatments. Similar to stem cells,CSCs also display high resistance to radiotherapy and chemotherapy with genotoxic agents. Thus, conventional therapy may shrink the tumor volume but cannot eliminate cancer. Eradiation of CSCs represents a novel therapeutic strategy. CSCs possess a highly efficient DNA damage response(DDR) system, which is considered as a contributor to the resistance of these cells from exposures to DNA damaging agents. Targeting of enhanced DDR in CSCs is thus proposed to facilitate the eradication of CSCs by conventional therapeutics. To achieve this aim, a better understanding of the cellular responses to DNA damage in CSCs is needed. In addition to the protein kinases and enzymes that are involved in DDR, other processes that affect the DDR including chromatin remodeling should also be explored.

Evaluation of KTJT-1,an early-maturity mutant of sweet sorghum acquired by carbon ions irradiation

Sweet sorghum has the potential of becoming a useful energy crop.An early-maturity mutant of sweet sorghum,KFJT-1,was obtained by carbon ions irradiation of KFJT-CK,a wild plant.In this paper,we evaluate the mutant from the length and fresh weight of radicle and leaves after seed germination,the growth rate at the elongation stage,and the internodal parameters under field trail condition.The results showed that the seedling growth of KFJT-1 was inhibited by carbon ions irradiation,and the leaf length,the fresh weight of radicle and leaves from KFJT-1 decreased by 15.32%,76.27%,and 27.08%than those of KFJT-CK,respectively.However,the growth rate of KFJT-1 on July 12,July 27 and August 1 increased by 16.19%,59.28%and26.87%,respectively,compared with the KFJT-CK.The stalk diameter,total biomass yield and sugar content of KFJT-1 was higher than those of KFJT-CK,despite that the plant height of KFJT-1 was significantly less than KFJT-CK(P < 0.05).In addition,KFJT-1 differed from KFJT-CK in the internodal length,weight and sugar content.In conclusion,the early-maturity mutant of KFJT-1 will be a promising variety for sweet sorghum industrialization in Gansu province,China.

Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways

Non-targeted effect is an important complement to the classical target theory of radiation biology which takesnuclear genomic DNA as the core target. The principle of radiation target theory is to assume that an organism orcell has one or more sensitive points or targets, hit and inactivation of which directly by radiation leads toconsiderable damage and the death event. Recent findings indicate that not only cell nucleus but also othercellular parts can be considered as possible targets. Mitochondrion is considered as a critical organelle where thenon-targeted effect is initiated. A series of recent studies have provided substantial evidence and solid data whichprofoundly facilitate the understanding of radiation-induced non-targeted effects emitted from mitochondrion inthe irradiated cells, such the major apparent performances, signaling pathways and biological significance.Mitochondrial genome is more sensitive to genotoxic than nuclear genome. Ionizing radiation can induce mtDNAsdouble-strand breaks directly or indirectly via increased mitochondrial ROS. Under stress conditions, mitochondrial DNA (mtDNA) fragments are released into the cytoplasm. The cytosol mtDNAs are sensed by cGAS andAIM2 proteins and they activate the corresponding signaling pathways, generating relevant inflammatory andimmune responses. These newly developed mitochondrial DNA-initiating pathways may boost the development oftargeted therapies for preventing normal tissue toxicity as well as radio-immunotherapy, an emerging trend forcancer therapies. Here we focus and discuss the mechanisms and biological significance of mtDNA-triggeringcGAS/AIM2 signaling pathways of immune response from the aspect of non-targeted effect of radiation.