Effect of combined treatment with radiation and low dose etoposide on cell survival.
BACKGROUND
To improve the radiotherapy results, we evaluated etoposide as an effective radiosensitizer by using cultured cell-lines.


METHODS
Four cell lines having different doubling times (DT) were used: V79 (Chinese hamster fibroblasts, DT = 9 hours), (1), T24 (human bladder cancer, DT = 19 hours) (2), MDA-MB231 (human breast cancer, DT = 25-30 hours) (3) and RMG1 (human ovarian cancer, DT = 50 hours) (4). Cell survival was determined by colony assay and cell cycle analysis was performed by flow-cytometry.


RESULTS
The survival curves showed RMG1 to be the most radiosensitive, followed by MDA-MB231, T24, and V79. V79 was most chemosensitive to etoposide, followed by T24, MDA-MB231 and RMG1. Neither 24-hours exposure to etoposide (< or = 0.05 microgram/ml) or 0.5-h exposure (< or = 1.0 microgram/ml) had any cell killing effect on any of the cell lines used. When the cells were irradiated after exposure to 1 microgram/ml of etoposide for 0.5 hours, no radiosensitization was observed in any of the cell lines except V79. Enhanced radiosensitivity was observed in V79 and T24 cells (which have a relatively short DT) when they were incubated with 0.05 microgram/ml etoposide for 24 hours but no enhanced effect was seen in MDA-MB231 or RMG1 cells (which have a relatively long DT).


CONCLUSIONS
It is suggested that a combination of radiation and etoposide may be useful in the treatment of rapidly growing cancer.
Shigematsu
N
N
Department of Radiology, School of Medicine, Keio University, 35-Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. shige@rad.med.keio.ac.jp
Kawata
T
T
Ihara
N
N
Kawaguchi
O
O
Kutsuki
S
S
Ishibashi
R
R
Kubo
A
A
Ito
H
H
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000532:radiotherapy
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D005047:Etoposide