Alterations in growth phenotype and radiosensitivity after fractionated irradiation of breast carcinoma cells from a single patient.
OBJECTIVE
To investigate growth regulation and radiosensitivity in surviving clonogens after fractionated irradiation.


METHODS
Four breast carcinoma cell lines isolated from the primary tumor (21NT, 21PT) and metastases (21MT-1, 21MT-2) of a single patient were exposed to cumulative radiation doses of 30 Gy yielding cell lines designated-IR with respect to their parent. The irradiated lines were then compared to their parent for serum-and growth factor-requirements under defined media conditions, ability to proliferate in soft agar, concentration of TGF-alpha in conditioned medium, and radiosensitivity.


RESULTS
The irradiated lines showed no change in proliferative doubling times under serum- and growth factor-supplemented media conditions. A single line, 21MT-1-IR, acquired a limited ability to proliferate in serum-and growth factor-deplete medium with a day 2-4 doubling time of 44.5 hr. Three lines, 21MT-1-IR, 21MT-2-IR, and 21NT-IR, formed colonies in soft agar in contrast to none of the unirradiated parent lines. There were significant 6-8 fold increases in conditioned media TGF-alpha concentrations for 21MT-2-IR and 21NT-IR cells. The 21MT-1-IR and 21NT-IR cells were significantly less radiosensitive than their respective parent lines. This decrease in radiosensitivity appeared to be at least partially mediated by a released factor as the radiosensitivity of 21MT-1 cells was significantly decreased by pre-incubation with conditioned medium from 21MT-1-IR cells.


CONCLUSIONS
Radiation-induced changes in growth phenotype vary with respect to clonal origin of the cell line and may influence the radiosensitivity of surviving clonogens after fractionated treatment.
Wazer
D E
DE
Department of Radiation Oncology, Tufts University School of Medicine, New England Medical Center, Boston, MA 02111.
Joyce
M
M
Jung
L
L
Band
V
V
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010641:Phenotype; D011836:Radiation Tolerance / Q000502:physiology*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000528:radiation effects*
D016211:Transforming Growth Factor alpha