Proliferative inhibition of human breast carcinoma cells by high concentration estradiol does not alter radiosensitivity.
The proliferation of ER+ malignant mammary epithelial cells (MMEC), MCF-7 and T-47D, was markedly inhibited by 10 microM 17 beta-estradiol (E2), while the ER- line, MDA-MB-231, was minimally affected. This concentration of E2 did not alter the proportion of non-viable cells or the plating efficiency. The decrease in proliferation was not associated with any consistent alteration in the cell kinetic profile between lines, though there was clearly no dominant cell cycle re-assortment after a two day incubation. Colony forming ability after exposure to ionizing irradiation was compared for proliferating and confluent MMEC to cells incubated in 10 microM E2 for two days. The presence of E2 resulted in no significant differences for any of the linear quadratic curve fitting parameters or for mean inactivation doses for both subconfluent and confluent cultures. Further, 10 microM E2 had no effect on the ability of cells to recover from split radiation fractions. There were no differences in the amount of DNA single strand break induction with E2, but there was a significant shortening in the repair halftime with E2 for the ER- MDA-MB-231 cells. Though high concentrations of E2 can markedly inhibit the proliferation of ER+ MMEC, this does not alter sensitivity to ionizing irradiation.
Wazer
D E
DE
Department of Radiation Oncology, New England Medical Center Hospitals, Tufts University School of Medicine, Boston, Massachusetts.
Joyce
M
M
Solares
G
G
Schmidt-Ullrich
R
R
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D011836:Radiation Tolerance / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000032:analysis; D014407:Tumor Cells, Cultured
D011960:Receptors, Estrogen; D004958:Estradiol