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Title: In vitro sensitivity of normal and hereditary retinoblastoma fibroblasts to DNA-damaging agents

We investigated the ability of nine fibroblast cell strains from patients with the hereditary form of retinoblastoma (RB) to handle various types of DNA-damaging agents and compared the results with those obtained in nine normal strains. Cell strains were exposed to gamma-radiation, which causes DNA scission; actinomycin D, a DNA-intercalating agent; and mitomycin C, a bifunctional alkylating agent leading to DNA-DNA cross-linking. Cell strains were studied for their ability to survive in a cytotoxicity assay. Nine normal strains exhibited a mean D0 (inverse of the slope of the straight line portion of the survival curve) of 134-178 cGy after radiation exposure, compared to a range of 119-186 cGy in the nine RB strains (P = 0.33). Similarly, exposure to actinomycin D led to D0 values of 0.024-0.069 microgram/ml in the nine normal strains and D0 values of 0.016-0.067 microgram/ml in the RB strains (P = 0.64). The nine RB strains did exhibit a small overall increase in sensitivity after exposure to mitomycin C, with D0 values ranging from 0.14-0.32 microgram/ml versus 0.19-0.66 microgram/ml in the nine normal strains (P = 0.002); however, when the two most resistant normal strains were excluded from analysis, results were similar. Three RB cell strainsmore » derived from individuals who had either developed second cancers or who had a family history of additional sarcomas consistently exhibited increases in sensitivity to all three DNA-damaging agents studied compared with other hereditary RB cell strains as well as normal strains. The results suggest that normal human fibroblast cell strains exhibit a wide response to DNA-damaging agents, especially chemical agents. Most hereditary RB strains exhibit sensitivity well within the normal range; however, strains from RB patients predisposed to second cancers exhibit increases in sensitivity to DNA-damaging agents.« less
Authors:
;
Publication Date:
OSTI Identifier:
6928453
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cancer Res.; (United States)
Research Org:
Univ. of Minnesota Hospitals, Minneapolis
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; DNA; DAMAGE; FIBROBLASTS; SENSITIVITY; ACTINOMYCIN; ALKYLATING AGENTS; DNA REPAIR; GAMMA RADIATION; GLIOMAS; IN VITRO; MITOMYCIN; NEOPLASMS; PATIENTS; RADIOSENSITIVITY; RETINA; ANIMAL CELLS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTIMITOTIC DRUGS; ANTINEOPLASTIC DRUGS; BIOLOGICAL RECOVERY; BIOLOGICAL REPAIR; BODY; BODY AREAS; CONNECTIVE TISSUE CELLS; DISEASES; DRUGS; ELECTROMAGNETIC RADIATION; EYES; FACE; HEAD; IONIZING RADIATIONS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; RADIATIONS; RECOVERY; REPAIR; SENSE ORGANS; SOMATIC CELLS 560120* -- Radiation Effects on Biochemicals, Cells, & Tissue Culture; 560300 -- Chemicals Metabolism & Toxicology