화학공학소재연구정보센터
Journal of Physical Chemistry B, Vol.115, No.16, 4843-4855, 2011
Mechanisms of Direct Radiation Damage to DNA: The Effect of Base Sequence on Base End Products
It has been generally assumed that product formation in DNA damaged by ionizing radiation is relatively independent of base sequence, i.e., that the yield of a given product depends primarily on the chemical properties of each DNA constituent and not on its base sequence context. We examined this assumption by comparing direct-type end products produced in films of d(CTCTCGAGAG)(2) with those produced in films of d(GCACGCGTGC)(2). Here we report the product yields in d(CTCTCGAGAG)(2) hydrated to Gamma = 2.5 and 15, where Gamma is the hydration level given in moles of H2O/mole of nucleotide. Of the 17 products monitored by GC/MS, seven exhibited statistically significant yields: 8-oxoGua, 8-oxoAde, 5-OHMeUra, 5,6-diHUra, 5,6-diHThy, 5-OHCyt, and 5-OHUra. These yields at Gamma = 2.5 are compared with the yields from our previously reported study of d(GCACGCGTGC)(2) (after projecting the yields to a CG/AT ratio of 1). The ratio of projected yields, d(CTCTCGAGAG)(2) divided by d(GCACGCGTGC)(2), are 1.3 +/- 0.9, 1.8 +/- 0.3, 1.6 +/- 0.6, 11.4 +/- 4.7, 0.2 +/- 0.1, >28, and 0.8 +/-1.1, respectively. Considering just d(CTCTCGAGAG)(2), the ratios of yields at Gamma = 2.5 divided by yields at Gamma = 15 are 0.7 +/- 0.2, 0.5 +/- 0.1, 2.3 +/- 4.0, 3.4 +/- 1.2, 3.5 +/- 3.3, 1.2 +/- 0.2, and 0.4 +/- 0.2, respectively. The effects of sequence and hydration on base product yields are explained by a working model emphasizing the difference between two distinctly different types of reaction: (i) radical reactions that progress to nonradical intermediates and product prior to dissolution and (ii) reactions that stem from radicals trapped in the solid state at room temperature that go onto yield nonradical product after sample dissolution. Based on these findings, insights into rates of hole and excess electron-transfer: relative to rites of proton transfer are discussed.