Title

Fpg protein releases a ring-opened N-7 guanine adduct from DNA that has been modified by sulfur mustard

UMMS Affiliation

Department of Pharmacology and Molecular Toxicology

Date

5-1-1997

Document Type

Article

Subjects

Adenine; Alkylation; Carcinogens; DNA Adducts; DNA-Formamidopyrimidine Glycosylase; Escherichia coli; *Escherichia coli Proteins; Guanine; Mustard Gas; N-Glycosyl Hydrolases

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Transfection of the Escherichia coli fpg gene into Chinese hamster ovary cells has been reported to enhance survival after exposure to aziridine (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 possibility that Fpg protein would offer protection from other agents that alkylate the N-7 position of guanine. Since the major adduct formed by sulfur mustard in DNA is 7-hydroxyethyl-thioethylguanine (HETEG), we have investigated the action of Fpg protein on the ring-opened form of this adduct (ro-HETEG). A substrate containing ro-HETEG was prepared by alkaline treatment of DNA modified by [14C]sulfur mustard. Fpg protein purified from an over-producing strain of E. coli released ro-HETEG 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-methylguanine. Thus, Fpg protein acts efficiently on ro-HETEG, and may offer some protection against the toxic action of sulfur mustard.

Rights and Permissions

Citation: Carcinogenesis. 1997 May;18(5):1035-8.

Related Resources

Link to article in PubMed

Journal Title

Carcinogenesis

PubMed ID

9163692