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
 

Sensitivity of human cell strains having different abilities to repair O6-methylguanine in DNA to inactivation by alkylating agents including chloroethylnitrosoureas

Journal Article · · Cancer Res.; (United States)
OSTI ID:6799524
; ; ; ; ;

In order to investigate the mechanisms of cellular damage by alkylating agents, human fibroblasts and tumor cell strains having different sensitivities to killing by N-methyl-N'-nitro-N-nitrosoguanidine (and different abilities to repair O6-methylguanine (O6mGua) in their DNA) were treated with other alkylating agents. Methyl methanesulfonate, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea, and N-ethyl-N'-nitro-N-nitrosoguanidine gave rise to sensitivity differences, but the differences were less than those observed with N-methyl-N'-nitro-N-nitrosoguanidine. After treatment with UV light, the strains showed similar survival. The data show that the DNA repair mechanism(s) responsible for the differential survival of the strains after N-methyl-N'-nitro-N-nitrosoguanidine treatment probably play(s) a role in repairing DNA damage produced by methyl methanesulfonate, N-ethyl-N'-nitro-N-nitrosoguanidine, BCNU, and 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea but not that produced by UV. Furthermore, the results support the idea that a breakdown product of BCNU, that does not cause damage repairable by O6mGua repair mechanisms, contributes to the lethal effects due to BCNU-produced DNA-damage that is repairable by O6mGua repair mechanisms. The survival data, along with nucleoid sedimentation and adenovirus host-cell reactivation data, are consistent with the hypothesis that the lesion(s) lethal to tumor cells defective in O6mGua DNA repair are lesions in which DNA oxygen atoms are alkylated.

Research Organization:
NCI-Frederick Cancer Research Facility, MD
OSTI ID:
6799524
Journal Information:
Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 44:6; ISSN CNREA
Country of Publication:
United States
Language:
English

Similar Records

Postreplication repair and the susceptibility of Chinese hamster cells to cytotoxic and mutagenic effects of alkylating agents
Journal Article · Wed Oct 01 00:00:00 EDT 1980 · Proc. Natl. Acad. Sci. U.S.A.; (United States) · OSTI ID:6756987
Mutagenesis of Neisseria gonorrhoeae: absence of error-prone repair
Journal Article · Mon Oct 01 00:00:00 EDT 1984 · J. Bacteriol.; (United States) · OSTI ID:6109556
Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents
Journal Article · Sat Mar 31 23:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA) · OSTI ID:6904776

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BIOLOGICAL VARIABILITY
CONNECTIVE TISSUE CELLS
DNA REPAIR
ELECTROMAGNETIC RADIATION
ESTERS
FIBROBLASTS
INACTIVATION
MAMMALS
MAN
METHYL METHANESULFONATE
MUTAGENS
NITROSO COMPOUNDS
NITROSOUREAS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PRIMATES
RADIATIONS
RECOVERY
REPAIR
SOMATIC CELLS
STRUCTURE-ACTIVITY RELATIONSHIPS
SULFONIC ACID ESTERS
TUMOR CELLS
ULTRAVIOLET RADIATION
VERTEBRATES