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Factors modifying 3-aminobenzamide cytotoxicity in normal and repair-deficient human fibroblasts

Journal Article · · J. Cell. Physiol.; (United States)
;
3-Aminobenzamide (3-AB), an inhibitor of poly(ADP-ribosylation), is lethal to human fibroblasts with damaged DNA. Its cytotoxicity was determined relative to a number of factors including the types of lesions, the kinetics of repair, and the availability of alternative repair systems. A variety of alkylating agent, UV or gamma irradiation, or antimetabolites were used to create DNA lesions. 3-AB enhanced lethality with monofunctional alkylating agents only. Within this class of compounds, methylmethanesulfonate (MMS) treatments made cells more sensitive to 3-AB than did treatment with methylnitrosourea (MNU) or methylnitronitrosoguanidine (MNNG). 3-AB interfered with a dynamic repair process lasting several days, since human fibroblasts remained sensitive to 3-AB for 36-48 hours following MMS treatment. During this same interval 3-AB caused these cells to arrest in G/sub 2/ phase. Alkaline elution analysis also revealed that this slow repair was delayed further by 3-AB. Human mutant cell defective in DNA repair differed in their responses to 3-AB. Greater lethality with 3-AB could be dependent on inability of the mutant cells to repair damage by other processes.
Research Organization:
Dana-Farber Cancer Institute, Boston, MA
OSTI ID:
5417310
Journal Information:
J. Cell. Physiol.; (United States), Journal Name: J. Cell. Physiol.; (United States) Journal Issue: 3 Vol. 120:3; ISSN JCLLA
Country of Publication:
United States
Language:
English

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Related Subjects

550300* -- Cytology
560121 -- Radiation Effects on Cells-- External Source-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
AMIDES
ANIMAL CELLS
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL KILLING
CONNECTIVE TISSUE CELLS
DISEASES
ELECTROMAGNETIC RADIATION
FIBROBLASTS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIATIONS
RECOVERY
REPAIR
SKIN DISEASES
SOMATIC CELLS
TELANGIECTASIS
TOXICITY
ULTRAVIOLET RADIATION
VASCULAR DISEASES
XP CELLS