Release of 7-alkylguanines from haloethylnitrosourea-treated DNA by E. coli 3-methyladenine-DNA glycosylase II.
Previous studies have related DNA modification by the haloethylnitrosoureas to their antitumor activity. Repair of this damage, particularly by O6-alkylguanine-DNA alkyltransferase, has been linked to tumor resistance by several previous investigations. We report here that E. coli 3-methyladenine-DNA glycosylase II can also remove several of the DNA modifications caused by the haloethylnitrosoureas. 7-Chloroethylguanine, 7-hydroxyethylguanine, and diguan-7-ylethane are all released into the supernatant from DNA modified by N-[2-chloroethyl-1,2-14C]-N'-cyclohexyl-N-nitrosourea. Release of diguan-7-ylethane is of particular interest since this entity evidently represents a DNA intrastrand cross-link. If a similar activity is present in mammalian cells, it might be an important source of resistance to the therapeutic action of the haloethylnitrosoureas.
D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D045647:DNA Glycosylases; D004926:Escherichia coli / Q000201:enzymology*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008130:Lomustine / Q000494:pharmacology*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*
C028317:7-(beta-chloroethyl)guanine; C035018:N(7)-hydroxyethylguanine; D006147:Guanine; C028316:diguanylethane; D008130:Lomustine; D004247:DNA; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases