Title

Protection against chloroethylnitrosourea cytotoxicity by eukaryotic 3-methyladenine DNA glycosylase

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

12-15-1993

Document Type

Article

Subjects

Animals; Cattle; Cell Survival; DNA; *DNA Glycosylases; DNA Repair; Drug Resistance; Ethylnitrosourea; Genes, Fungal; Kinetics; Mammals; N-Glycosyl Hydrolases; Saccharomyces cerevisiae

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

A eukaryotic 3-methyladenine DNA glycosylase gene, the Saccharomyces cerevisiae MAG gene, was shown to prevent N-(2-chloroethyl)-N-nitrosourea toxicity. Disruption of the MAG gene by insertion of the URA3 gene increased the sensitivity of S. cerevisiae cells to N-(2-chloroethyl)-N-nitrosourea, and the expression of MAG in glycosylase-deficient Escherichia coli cells protected against the cytotoxic effects of N-(2-chloroethyl)-N-nitrosourea. Extracts of E. coli cells that contain and express the MAG gene released 7-hydroxyethylguanine and 7-chloroethylguanine from N-(2-chloroethyl)-N-nitrosourea-modified DNA in a protein- and time-dependent manner. The ability of a eukaryotic glycosylase to protect cells from the cytotoxic effects of a haloethylnitrosourea and to release N-(2-chloroethyl)-N-nitrosourea-induced DNA modifications suggests that mammalian glycosylases may play a role in the resistance of tumor cells to the antitumor effects of the haloethylnitrosoureas.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11855-9.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

8265637