Differential cytotoxic activity of chemotherapy agents on colony-forming cells from human tumors and normal bone marrow in vitro.
We have compared the in vitro differential killing efficacy of doxorubicin, 5-fluorouracil, cis-platinum, etoposide, and bleomycin on human tumor cells in a new adhesive tumor cell culture system (ATCCS), and on normal bone marrow granulocyte-macrophage colony-forming units (GM-CFUC) in culture. All of the above chemotherapy agents were tested with continuous exposure against tumor cells and GM-CFUC. In addition, bleomycin was also tested with a short (60 min) exposure against GM-CFUC. In order to determine chemosensitivity against all five drugs, 48 tumor specimens from patients with heterogeneous tumor types were tested in the ATCCS. Each drug was tested at three different concentrations corresponding to their lethal doses against GM-CFUC. Our results show that all five drugs exhibited a dose-response relationship against tumor cells and GM-CFUC. Bleomycin also showed a pronounced GM-CFUC-sparing quality with 60-min exposure even at very high concentrations (86% survival of GM-CFUC at 10 micrograms/ml and 48% at 50 micrograms/ml). In addition, it has a high tumor response rate with continuous exposure at low concentrations (67% at GM-CFUC LD5 and 91% at LD40). These data suggest that the comparison of differential cytotoxicity of chemotherapy drugs between tumor cells and bone marrow cells may serve as a model to select agents suitable for in vitro chemotherapy of bone marrow for the purpose of autologous bone marrow transplantation. In particular, bleomycin appears very attractive and deserves further investigation.
Ajani
J A
JA
Blaauw
A A
AA
Spitzer
G
G
Baker
F L
FL
Tomasovic
B
B
Umbach
G
G
Thielvoldt
D
D
Zander
A R
AR
Dicke
K A
KA
D000970:Antineoplastic Agents / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity; D001943:Breast Neoplasms / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D005047:Etoposide / Q000633:toxicity; D005472:Fluorouracil / Q000633:toxicity; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008545:Melanoma / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D012509:Sarcoma / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects*
D000970:Antineoplastic Agents; D001761:Bleomycin; D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil