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

Journal Article · Mon Dec 01 04:00:00 EST 1986 · Cancer Res.; (United States)

OSTI ID:6928453

Woods, W G; Byrne, T D

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 strains 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.

• Research Organization: Univ. of Minnesota Hospitals, Minneapolis
• OSTI ID: 6928453
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States); ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300 -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACTINOMYCIN
ALKYLATING AGENTS
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
BODY AREAS
CONNECTIVE TISSUE CELLS
DAMAGE
DISEASES
DNA
DNA REPAIR
DRUGS
ELECTROMAGNETIC RADIATION
EYES
FACE
FIBROBLASTS
GAMMA RADIATION
GLIOMAS
HEAD
IN VITRO
IONIZING RADIATIONS
MITOMYCIN
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATIENTS
RADIATIONS
RADIOSENSITIVITY
RECOVERY
REPAIR
RETINA
SENSE ORGANS
SENSITIVITY
SOMATIC CELLS