Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Adaptive resynthesis of O/sup 6/-methylguanine-accepting protein can explain the differences between mammalian cells proficient and deficient in methyl excision repair

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
; ;

Mammalian cells have been classified as proficient (Mer/sup +/) or deficient (Mer/sup -/) in methyl excision repair in terms of their cytotoxic reactions to agents that form O/sup 6/-alkylguanine and their abilities to reactivate alkylated adenoviruses. O/sup 6/-Methylguanine (O/sup 6/MeGua) is considered to be a lethal, mutagenic, and carciogenic lesion. We measured the abilities of cell extracts to transfer the methyl group from an exogenous DNA containing O/sup 6/MeGua to acceptor protein. The constitutive level of acceptor activity was independent of the Mer phenotype and was approx. = 100,000 acceptor sites per cell. Treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) results in a dose-dependent decrease in the acceptor activity in extracts because the rapid reaction between endogenous O/sup 6/MeGua and acceptor protein makes the latter unavailable for further reaction. Treatment of cells with multiple low doses of MNNG results in the enhanced production of O/sup 6/MeGua-accepting protein in levels 2.5-fold above the constitutive values for Mer/sup +/ tumor cells and to approx. = 1.5-fold for Mer/sup +/ fibroblasts or Mer/sup -/ simian virus 40-transformed cells. Such treatments reduce the activities in Mer/sup -/ tumor cells and Chinese hamster cells. We concluded; (i) estimates of O/sup 6/MeGua in cellular DNA shortly after treatment may be seriously in error because of the rapid repair of this lesion, and (ii) the adaptive resynthesis of acceptor protein, not its constitutive level, is the important correlate of cell resistance to methylating agents.

Research Organization:
Brookhaven National Lab., Upton, NY
OSTI ID:
6652726
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 79:17; ISSN PNASA
Country of Publication:
United States
Language:
English

Similar Records

Extracts of chronic lymphocytic leukemia lymphocytes have a high level of DNA repair activity for O/sup 6/-methylguanine
Journal Article · Sun Aug 01 00:00:00 EDT 1982 · Proc. Natl. Acad. Sci. U.S.A.; (United States) · OSTI ID:5243229
Apparent lack of an O/sup 6/-methylguanine repair mechanism in the unicellular alga, Chlamydomonas ReinhardtII
Journal Article · Thu May 01 00:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) · OSTI ID:5118561
Lack of induction of O/sup 6/-methylguanine-DNA methyltransferase in mammalian cells treated with N-methyl-N'-nitro-N-nitrosoguanidine
Journal Article · Sat Dec 31 23:00:00 EST 1983 · Carcinogenesis; (United States) · OSTI ID:5877462

Related Subjects

550200 -- Biochemistry
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMAL CELLS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BIOSYNTHESIS
CONNECTIVE TISSUE CELLS
DNA
DOSE-RESPONSE RELATIONSHIPS
FIBROBLASTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
KINETICS
NITROSO COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PURINES
REACTION KINETICS
RECOVERY
REPAIR
SOMATIC CELLS
SYNTHESIS