FPG PROTEIN RELEASES A RING-OPENED N-7 GUANINE ADDUCT FROM DNA THAT HAS BEEN MODIFIED BY SULFUR MUSTARD

Citation
Qo. Li et al., FPG PROTEIN RELEASES A RING-OPENED N-7 GUANINE ADDUCT FROM DNA THAT HAS BEEN MODIFIED BY SULFUR MUSTARD, Carcinogenesis, 18(5), 1997, pp. 1035-1038
Citations number
12
Categorie Soggetti
Oncology
Journal title
ISSN journal
01433334
Volume
18
Issue
5
Year of publication
1997
Pages
1035 - 1038
Database
ISI
SICI code
0143-3334(1997)18:5<1035:FPRARN>2.0.ZU;2-7
Abstract
Transfection of the Escherichia coli fpg gene into Chinese hamster ova ry cells has been reported to enhance survival after exposure to aziri dine (C.Cussac and F.Laval, 1996, Nucleic Acids Res., 24, 1742-1746). This result suggests that Fpg protein protects cells from toxicity by removing ring-opened N-7 guanine adducts from DNA, and raises the poss ibility that Fpg protein would offer protection from other agents that alkylate the N-7 position of guanine. Since the major adduct formed b y sulfur mustard in DNA is 7-hydroxyethyl-thioethylguanine (HETEG), we have investigated the action of Fpg protein on the ring-opened form o f this adduct (ro-HETEG). A substrate containing ro-HETEG was prepared by alkaline treatment of DNA modified by [C-14]sulfur mustard. Fpg pr otein purified from an over-producing strain of E.coli released ro-HET EG from this substrate in an enzyme- and time-dependent manner, and at a rate that is similar to that at which it releases ring-opened 7-met hylguanine. Thus, Fpg protein acts efficiently on ro-HETEG, and may of fer some protection against the toxic action of sulfur mustard.