RELEASE OF SULFUR MUSTARD-MODIFIED DNA BASES BY ESCHERICHIA-COLI 3-METHYLADENINE DNA GLYCOSYLASE-II

The toxic effects of sulfur mustard have been attributed to DNA modifi cation with the formation of 7-hydroxyethylthioethyl guanine, 3-hydrox yethylthioethyl adenine and the cross-link, di-(2-guanin-7-yl-ethyl)su lfide. To investigate the action of bacterial 3-methyladenine DNA glyc osylase II (Gly II) on these adducts, calf thymus DNA was modified wit h [C-14]sulfur mustard and used as a substrate for Gly II. Gly II rele ases both 3-hydroxyethylthioethyl adenine and 7-hydroxyethylthioethyl guanine from this substrate. In comparison with the activity of Gly II towards methylated DNA, 3-hydroxyethylthioethyl adenine is released s omewhat more slowly than 3-methyladenine, while 7-hydroxyethylthioethy l guanine is released much more readily than 7-methylguanine. Glycosyl ase action may play a role in protecting cells from the toxic effects of sulfur mustard.