| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
DNA double strand breaks (DSBs) are the most critical DNA lesions for cell death. However, other lethal lesions such as DNA-protein cross-links (DPCs) and DNA interstrand cross-links (ICLs) are produced by DNA damaging agents. Here we estimated the roles of DPCs and ICLs in the lethal events of cells upon exposure to aldehydes and X-rays. DNA repair was essential for alleviating the cytotoxic effect of weakly toxic aldehydes such as saturated aldehydes. Our data also suggest that ICLs are the critical cytotoxic DNA damage induced by aldehydes. X-rays produced more DPCs in hypoxic tumors than in normoxic tumors. X-rays generated two types of DPC that differed according to their rate of removal from the genome. The half-lives of the rapidly removed components of DPCs and DSBs were similar, but those of the slowly removed components of DPCs were markedly different. The long half-life and abundance of the slowly removed DPCs may exert deleterious effects on cells in conjunction with DSBs.
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