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Lack of induction of O/sup 6/-methylguanine-DNA methyltransferase in mammalian cells treated with N-methyl-N'-nitro-N-nitrosoguanidine

Journal Article · · Carcinogenesis; (United States)
;

A synthetic DNA substrate containing O/sup 6/-methyl(8-/sup 3/H)-guanine was used to assay demethylation of the premutagenic base by O/sup 6/-methylguanine-DNA methyltransferase in extracts of HeLa cells, Chinese hamster ovary cells and normal rat kidney cells which had been treated with multiple doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). No induction of methyltransferase activity was observed in any of the cell lines tested. Constitutive levels of methyltransferase in cell lines proficient (Mex/sup +/) in O/sup 6/-methylguanine repair were decreased in a dose-dependent fashion by either single or multiple treatments with MNNG over a broad range of dose levels. Recovery of constitutive levels of activity required 24- to 48-h incubation periods. Repair deficient (Mex/sup -/) cell lines lacked both constitutive and inducible methyltransferase activity. 42 references, 4 figures, 1 table.

Research Organization:
Univ. of Tennessee-Oak Ridge Graduate School of Biomedical Sciences
DOE Contract Number:
W-7405-ENG-26
OSTI ID:
5877462
Journal Information:
Carcinogenesis; (United States), Journal Name: Carcinogenesis; (United States) Vol. 5:2; ISSN CRNGD
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
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
ANIMALS
AROMATICS
AZAARENES
BIOASSAY
BIOLOGICAL EFFECTS
BODY
CHO CELLS
DATA
DNA
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ENZYMES
EXPERIMENTAL DATA
GUANINE
HELA CELLS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INFORMATION
KIDNEYS
MAMMALS
NITROSO COMPOUNDS
NUCLEIC ACIDS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PURINES
RATS
RODENTS
TRANSFERASES
VERTEBRATES