RADIATION-INDUCED DNA-DAMAGE AS A FUNCTION OF HYDRATION .2. BASE DAMAGE FROM ELECTRON-LOSS CENTERS

The induction of base damage products in gamma-irradiated DNA, hydrate d between 2.5 and 32.8 moles of water per mole of nucleotide (Gamma), was investigated using the gas chromatography/mass spectrometry-select ed ion monitoring technique. In general, the yields of the measured ba se damage products were found to be dependent on the extent of the hyd ration when the DNA was irradiated under nitrogen. At low hydrations ( Gamma less than or equal to 13), the highest yields of the measured pr oducts were found for 7,8-dihydro-8-oxo-guanine, 5,6-dihydrothymine an d, to a lesser extent, 2,6-diamino-4-oxo-5-formamidopyrimidine, produc ts which are consistent with the base radicals found in low-temperatur e ESR studies. At higher hydrations (Gamma less than or equal to 13), changes in DNA conformation and an increase in the attack of bulk wate r radicals on DNA play a significant role in the formation of radiatio n-induced DNA base damage products. Additional findings in our study i nclude: (1) the sum of the yields of the products formed from electron -loss centers is greater than the sum of the yields of the products fo rmed from electron-gain centers, indicating that there might be other electron-gain products which have not been identified; (2) the combine d yield for the base damage products and the release of unaltered base s at Gamma less than or equal to 13 is constant, implying that radiati on damage in the tightly bound water molecules of the primary hydratio n layer causes DNA damage (quasi-direct effect) that is similar to the damage caused by direct ionization of the DNA (direct effect); and (3 ) the yields of the individual base damage products that were formed f rom electron-loss centers can be modeled on the basis of both the know n reactions that lead to the formation of the initial charged base rad icals in irradiated DNA, and the known reactions that involve the conv ersion of these initial DNA radicals into their respective nonradical end products. (C) 1996 by Radiation Research Society