Studies on the Chemical Basis of Cellular Radiosensitization by 5-bromouracil Substitution in DNA

Abstract

SummaryPulse- and steady-state radiolysis studies show two major differences in the radiation chemistry of aqueous solutions of E. coli DNA (DNA) and bromouracil substituted DNA (BU-DNA): on exposure of N2-saturated solutions to low doses of radiation the absorbance of BU-DNA increases while that of DNA decreases; the free radicals formed by OH· attack on BU-DNA decay more rapidly than those on DNA. The differences are explained with the help of results from the accompanying paper by a mechanism involving conversion of the BU moiety of BU-DNA to a uracil (U) moiety by reaction of BU-DNA with organic free radicals. Uracil-5-yl radicals are formed which may abstract H· from neighbouring deoxyribose moieties to give uracil and a radical which may lead to a single-strand break. A hypothesis for BU radiosensitization, based on these and earlier results, account for (a) more DNA base damage and (b) more single-strand breaks in BU-DNA than in DNA; and (c) formation of U in BU-DNA.