8-ARYLGUANINE ADDUCTS FROM ARENEDIAZONIUM IONS AND DNA

Arenediazonium ions (ArN2+) are genotoxic though the source of their g enotoxicity is unknown. The present studies were undertaken to determi ne if reductive decomposition of ArN2+ to aryl radicals (Ar-.) in the presence of calf thymus DNA (ctDNA) or in cells results in the formati on of DNA adducts. We found that when arenediazonium ions of the gener al structure p-X-ArN2+ (X = CH3, CH2OCH3, CH2OH) are allowed to react with ctDNA or incubated with cells under conditions that produce p-X-A r-., DNA adducts are formed with guanine. The structure of the adduct is the C-8-substitution product derived from guanine and p-X-Ar-., For mation of p-X-Ar-. was determined by ESR spin-trapping with 5,5-dimeth yl-1-pyrroline N-oxide (DMPO). The extent of C-8-arylguanine adduction was measured by high performance liquid chromatography (HPLC) analysi s of the DNA hydrosylate and comparison with authentic synthetic stand ards. The C-8-arylguanine adducts observed to form may be important in regard to the genotoxicity of ArN2+, though other DNA adducts such as the N-6-triazene of adenine or C-8-aryladenine adducts can form. Fina lly, though the formation of C-8-arylguanine adducts from arenediazoni um ions has been proposed, this is the first report demonstrating thei r formation in DNA.