Mechanisms for radiation damage in DNA. Progress report, June 1, 1994--May 31, 1995
In this project we have proposed several mechanisms for radiation damage to DNA and its constituents, and have detailed a series of experiments utilizing electron spin resonance spectroscopy, HPLC, GC-mass spectroscopy and ab initio molecular orbital calculations to test the proposed mechanisms. The results from these various techniques have resulted in an understanding of consequences of radiation damage to DNA from the early ionization event to the production of non-radical lesions (discussed in detail in Comprehensive Report). In this year`s work we have found the hydroxyl radical in DNA`s hydration layer. This is an important result which impacts the hole transfer hypothesis and the understanding of the direct vs. indirect effect in DNA. Further we have found the first ESR evidence for sugar radicals as a result of direct radiation damage to DNA nucleotides in an aqueous environment. This is significant as it impacts the biological endpoint of radiation damage to DNA and suggests future work in DNA. Work with DNA-polypeptides show clear evidence for electron transfer to DNA from the polypeptide which we believe is a radioprotective mechanism. Our work with ab initio molecular orbital theory has gain insight into the initial events of radiation damage to DNA. Ab initio calculations have provided an understanding of the energetics involved in anion and cation formation, ion radical transfer in DNA as well as proton transfer with DNA base pair radical ions. This has been extended in this year`s work to new, more accurate values for the electron affinities of the DNA bases, understanding of the relative stability of all possible sugar radicals formed by hydrogen abstraction on the deoxyribose group, hydration effects on, thiol radioprotectors, and an ongoing study of radical intermediates formed from initial DNA ion radicals. During this fiscal year five articles have been published, three are in press, two are submitted and several more are in preparation.
- Research Organization:
- Oakland Univ., Rochester, MI (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- FG02-86ER60455
- OSTI ID:
- 83812
- Report Number(s):
- DOE/ER/60455--8; ON: DE95014982
- Country of Publication:
- United States
- Language:
- English
Similar Records
Mechanisms for radiation damage in DNA. Progress report, June 1, 1992--May 31, 1993
Mechanisms for radiation damage in DNA