Sensitivity of human cell strains having different abilities to repair O6-methylguanine in DNA to inactivation by alkylating agents including chloroethylnitrosoureas
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), Vol. 44:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DNA REPAIR
INACTIVATION
METHYL METHANESULFONATE
BIOLOGICAL EFFECTS
NITROSOUREAS
ULTRAVIOLET RADIATION
ANIMAL CELLS
BIOLOGICAL VARIABILITY
FIBROBLASTS
MAN
STRUCTURE-ACTIVITY RELATIONSHIPS
TUMOR CELLS
ANIMALS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CONNECTIVE TISSUE CELLS
ELECTROMAGNETIC RADIATION
ESTERS
MAMMALS
MUTAGENS
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PRIMATES
RADIATIONS
RECOVERY
REPAIR
SOMATIC CELLS
SULFONIC ACID ESTERS
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)