IDENTIFICATION OF ADENINE ADDUCTS FORMED IN REACTION OF CALF THYMUS DNA WITH MUTAGENIC CHLOROHYDROXYFURANONES FOUND IN DRINKING-WATER

Calf thymus DNA was reacted with the extremely potent bacterial mutage n -chlora-4(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and the stru cturally related compounds 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA) and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF). The chromatogra ms of the HPLC analyses of the DNA hydrolysates showed peaks that repr esented adduct;ed base moieties. it was possible to establish the stru ctures of the adducts by comparing UV spectra and chromatographical pr operties of the DNA adducts with known adenosine and 2'-deoxyadenosine adducts. The DNA adduct produced by MX was identified as 3-(2'-deoxyr ibofuranosyl-N-6-adenosinyl)propenal (M(1)A-dR). It was calculated tha t 1 nucleotide/10(5) nucleotides was converted to M(1)A-dR. The same a dduct was formed also in the reaction of MX with 2'-deoxyadenosine (yi eld 0.01%). The M(1)A-dR adduct may play a role in the mutational even ts induced by MX in Salmonella typhimurium strain TP2428, The adducts produced in the reactions of MCA and MCF with DNA were identified as ' -deoxyribofuranosyl)-7-formylimidazo[2,1-i]purine (epsilon cA-dR) and -(2'-deoxyribofuranosyl-N-6-adenosinyl)-3-formyl-3 -butenoic acid (fba A-dR), respectively. The yield of epsilon cA-dR was 5 adducts/10(6) nu cleotides and of fbaA-dR 4 adducts/10(5) nucleotides. The biological s ignificance of these adducts is unkown.