Surgical adjuvant therapy in colon carcinoma: a human tumor spheroid model for evaluating radiation sensitizing agents

Journal Article · Fri May 15 00:00:00 EDT 1981 · Cancer (Philadelphia); (United States)

DOI:https://doi.org/10.1002/1097-0142(19810515)47:10<2349::AID-CNCR2820471005>3.0.CO;2-L· OSTI ID:5440748

Barone, R M; Calabro-Jones, P; Thomas, T N; Sharp, T R; Byfield, J E

HT-29 human colon tumor cells growing as spheroids have been evaluated as a model system for measuring the response of human colon tumor cell to antineoplastic agents. HT-29 cells have been capacity to form spheroids up to 1 mm or more in diameter when grown in spinner culture. The multicellular HT-29 spheroids develop hypoxic centers reflecting the cellular conditions found in human cancer treatment, i.e., nutritionally deficient hypoxic cells that are felt to be a significant source of both radiation and chemotherapy clinical treatment failures. Spheroids of increasing size were radiated and then dispersed into single cells for colony survival assay. Compared with irradiated single cell suspensions, the spheroid cells demonstrated a significant increase in radioresistance. Growing spheroids developed a complex radiation survival curve which was variable with respect to size of the spheroid. The drug 5-Fu was studied to examine in a preliminary fashion its interaction with these resistant cell fractions. In direct cytotoxicity assay, 5-fluorouracil (5-FU) exhibited both cytotoxic and cytostatic effects when the drug was present at a concentration greater than 0.4 microgram/ml. The interaction of 5-FU with x-rays in the HT-29 spheroids was complex and dependent on the type of assay employed (spheroid size versus clonogenicity). The effect of allopurinol, an agent that protects cells from 5-FU toxicity was examined. Allopurinol at a concentration of 100 microgram/ml was found to protect these human colonic carcinoma cells from the cytotoxic effects of 5-FU under conditions resembling those found in vivo. Overall, this HT-29 spheroid system appears to b an interesting model for studying a variety of drug/x-ray interactions in vitro and may prove capable of answering specific questions of preclinical and clinical relevance.

• OSTI ID: 5440748
• Journal Information: Cancer (Philadelphia); (United States), Vol. 47:10
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTINEOPLASTIC DRUGS
RADIOSENSITIVITY EFFECTS
TUMOR CELLS
RADIOSENSITIVITY
ANOXIA
BIOLOGICAL MODELS
CARCINOMAS
CELL CULTURES
DOSE-RESPONSE RELATIONSHIPS
LARGE INTESTINE
SPHEROIDS
SURVIVAL CURVES
X RADIATION
ANIMAL CELLS
BODY
DIGESTIVE SYSTEM
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
GASTROINTESTINAL TRACT
INTESTINES
IONIZING RADIATIONS
NEOPLASMS
ORGANS
RADIATIONS
560121* - Radiation Effects on Cells- External Source- (-1987)
550603 - Medicine- External Radiation in Therapy- (1980-)