The objectives of this study were to evaluate the protective effects of 
amifostine against paclitaxel-induced toxicity to normal and malignant human 
tissues. Haematopoietic progenitor colony assays were used to establish the 
number of CFU-GEMM and BFU-E colonies after incubation with WR-1065 alone, 
Amifostine alone, paclitaxel (2.5 or 5 microM) +/- WR-1065 or amifostine. MTT 
and alkaline elution assays evaluated the in vitro growth inhibitory and DNA 
damaging effects, respectively, of paclitaxel with or without amifostine against 
normal human fibroblasts and human non-small cell lung cancer (NSCLC) cells. 
This combination was also evaluated in vivo using severe combined immune 
deficient (scid) mouse models of early (non-palpable tumours) and advanced 
(palpable tumours) human ovarian cancer. Human 2780 ovarian cancer cells were 
inoculated subcutaneously while paclitaxel and amifostine were administered 
intraperitoneally. A brief exposure (15 min) to amifostine not only protected 
human haematopoietic progenitor colonies from paclitaxel toxicity, but 
stimulated the growth of CFU-GEMM and BFU-E beyond control values. Amifostine 
protected normal human lung fibroblasts from paclitaxel-induced cytotoxicity and 
DNA single-strand breaks. However, paclitaxel cytotoxicity and DNA single-strand 
breaks were actually enhanced by pretreatment with amifostine in the NSCLC 
model. Importantly, amifostine did not interfere with paclitaxel antitumour 
activity even with prolonged exposure (24.5 h) of the lung cancer cells to high 
concentrations (1.2 mM) in vitro or following five repetitive high doses (200 
mg/kg) given to scid mice with human ovarian cancer xenografts. Indeed, under 
certain circumstances, amifostine resulted in sensitisation of tumour cells to 
paclitaxel. Our results confirm previous reports of the ability of amifostine to 
protect normal tissues from the toxic effects of chemotherapy drugs and now 
extend these observations to paclitaxel.