Intrinsic and extrinsic heterogeneity in the responses of parent and clonal human colon carcinoma xenografts to photon irradiation

Journal Article · Sat Sep 01 04:00:00 EDT 1984 · Cancer Res.; (United States)

OSTI ID:6348486

Leith, J T; Bliven, S F; Lee, E S; Glicksman, A S; Dexter, D L

Responses to photon irradiation of xenografted human colon tumors derived from the heterogeneous DLD-1 line or its derivative A and D subpopulations were determined using excision assay and tumor regrowth delay assays. Differential responses among the three xenografted carcinomas were demonstrated. Clone A tumors treated with up to 17.5 Gy showed no actual regression below pretreatment volume. In contrast, clone D tumors were sensitive to doses as low as 3.5 Gy, and tumor volumes were reduced by 65% with a dose of 17.5 Gy. The responses of DLD-1 tumors were intermediate between the clone A and clone D tumor responses. Data indicate that the DLD-1 tumors were the most resistant, with clone A of intermediate sensitivity, clone D being the most sensitive tumor. In addition to the interclonal diversity among xenograft lines, intraclonal variation was also observed with clone A (but not clone D or DLD-1) tumors. A biphasic survival curve of cells from clone A xenografts irradiated in air-breathing hosts clearly indicated a minority (approximately 3%) subpopulation of hypoxic cells. Similar results indicating a small percentage of hypoxic cells in clone A solid tumors were obtained from the tumor regrowth delay studies. Also, excision assay data from experiments in which the heterografted carcinomas were irradiated under anoxic conditions support the interpretation that clone A tumors contain a small fraction of hypoxic cells. This study indicates that: (a) heterogeneity in vivo to ionizing radiation exists in the DLD-1 system; and (b) intraclonal variation occurs in vivo due to extrinsic (e.g., environmental hypoxia) factors, such that the intrinsic radioresistance of a subpopulation (clone A) of a heterogeneous human tumor can be further increased.

• Research Organization: Rhode Island Hospital, Providence
• OSTI ID: 6348486
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 44:9; ISSN CNREA
• Country of Publication: United States
• Language: English

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560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANOXIA
BEAMS
BODY
CARCINOMAS
CELL CULTURES
CLONE CELLS
COMPARATIVE EVALUATIONS
DIGESTIVE SYSTEM
DISEASES
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
EXTERNAL IRRADIATION
GASTROINTESTINAL TRACT
GRAFTS
INTESTINES
IRRADIATION
LARGE INTESTINE
NEOPLASMS
NONMETALS
ORGANS
OXYGEN
PHOTON BEAMS
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
TRANSPLANTS