THE ROLE OF SUGAR IN RADIATION-INDUCED CROSSLINKS IN DNA

One of the major areas of interest has been the effect of radiation on DNA since these effects have been in general successfully correlated to the radiation-induced lethality, mutagenesis, and possibly carcinogenesis. The chemistry of pyrimidine is represented by thymine (T) one of the four DNA bases and used in this work as a model component. Deoxyribose, dR, was used as a model for the reaction of the sugar in DNA. In this work the reactions of: d(')R + d(')R (--->) dR-dR. d(')R + (')T-OH (--->) dR-T-OH. d(')R + (')Phe-OH (--->) dR-Phe-OH. were investigated for possible crosslinks which would represent a model for intra-DNA and DNA-protein crosslinks. These reactions have not been investigated before. The products were isolated and identified using capillary gas chromatography, and capillary gas chromatography-mass spectrometry. In addition, the yields of crosslinks between thymine deoxyribose and phenylalanine deoxyribose and deoxyribose deoxyribose were determined by gas chromatography. Mechanisms of their formation are discussed in detail. As a means of standardizing the irradiations of DNA solutions, special radiochromic dye solutions in several organic solvents have been investigated as standard dosimeters in this work. These radiation sensors are well-behaved chromophoric systems, based on the formation of highly colored carbonium ions from leuco triphenyl- methane dyes (e.g., pararosaniline leucocyanide or some of its analogs). (NH(,2)C(,6)H(,4))(,3)C-CN -- (--->) NH(,2)C(,6)H(,4)=C=(NH(,2)C(,6)H(,4))(,2) + C(')N. The great advantage of developing and using these standard solutions for the dosimetry is that their radiation absorption cross-sections match closely those of the DNA solutions, thus leading to highly accurate radiation absorbed dose. A choice has been made in terms of the most accurate chemical dosimeter for the purpose of this research, by examining the uncertainty probabilities of meas- uring radiation chemical yields (G-value) of radiolytic dye formation, as well as linear molar absorption coefficients ((epsilon)) of the radiation-induced species. After establishing the G-values of dye formation using gamma radiation from a ('60)Co source, kinetics studies have been made for this dye formation in selected solvents in terms of first-order rate constants.