In vitro effect of amifostine on haematopoietic progenitors exposed to carboplatin and non-alkylating antineoplastic drugs: haematoprotection acts as a drug-specific progenitor rescue.
We evaluated the protective ability of amifostine on peripheral blood mononuclear cell (PBMC)-derived colony-forming unit (CFU) and PB CD34+ cells which were previously exposed in vitro to etoposide, carboplatin, doxorubicin and taxotere. Amifostine pretreatment protected PBMC-derived CFU from the toxic effect of etoposide, carboplatin and taxotere. A significant detrimental effect was exerted by amifostine on the growth of doxorubicin-treated PBMC-derived CFU. Liquid cultures of PB CD34+ cells reproduced faithfully the effects observed on growth of PBMC-derived CFU and confirmed amifostine chemoprotection against etoposide and carboplatin with its detrimental effect on doxorubicin-treated progenitors. Combining the data of viable cell count, cytometric estimation of apoptosis, cell cycle and viable cell replication rate, we found that amifostine protects from etoposide and carboplatin toxicity mainly through a mechanism of cell rescue. Conversely, the detrimental effect of amifostine on the growth of doxorubicin-treated PB CD34+ cells is apparently due to an increased G2/M arrest. In conclusion, amifostine protects haematopoietic progenitors from etoposide, carboplatin and taxotere. Progenitor rescue is the mechanism through which amifostine reduced etoposide and carboplatin toxicity.
Pierelli
L
L
Cattedra di Ematologia, Catholic University, Rome, Italy.
Scambia
G
G
Fattorossi
A
A
Bonanno
G
G
Battaglia
A
A
Perillo
A
A
Menichella
G
G
Panici
P B
PB
Leone
G
G
Mancuso
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000494:pharmacology; D004999:Amifostine / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis; D016190:Carboplatin / Q000009:adverse effects*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000077143:Docetaxel; D004317:Doxorubicin / Q000009:adverse effects / Q000378:metabolism; D005047:Etoposide / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D017239:Paclitaxel / Q000009:adverse effects / Q000031:analogs & derivatives; D043823:Taxoids; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D005047:Etoposide; D004317:Doxorubicin; D016190:Carboplatin; D004999:Amifostine; D017239:Paclitaxel