No abstract

METHODS There are three stages in the procedure: taking blood into PHA, centrifuging the blood and incubating the cells that remain suspended. These stages will be described separately. Each maneuvre was carried out using standard sterile precautions.Blood Taking.-The subjects, healthy men aged 20-38 years, had fasted for at least 3 hr. to avoid excessive lipamia. Approximately 300 ml. of blood was withdrawn from an antecubital vein directly into a bottle containing 30 mg. dry heparin. Care was taken to avoid frothing. Aliquots (20 ml.) of this blood were transferred to McCartney bottles. These bottles had siliconed rubber washers in their caps and each contained 04 ml. of a solution of PHA made up as follows: 5 ml. distilled water was added to each vial of PHA (phytohaomagglutinin P. Difco *) to dissolve the dry

Hydroxymethylacylfulvene (HMAF) is a novel agent with alkylating activity and is a potent inducer of apoptosis that is currently undergoing Phase II clinical trials for prostate cancer. This study explored the pro-apoptosis and anti-proliferative potential of HMAF in combination with gamma radiation in human prostate tumor cell lines. Apoptosis was assessed based on the generation of fragmented DNA, a terminal transferase flow cytometry assay, and cell morphology. In each of the tumor cell lines examined, radiation alone induced a marginal level of apoptosis, even after a prolonged 48-h incubation after exposure. In contrast, HMAF alone was a potent inducer of apoptosis in prostate tumor cells but not in normal cells. Marked levels of apoptosis in tumor cells were also observed for the combination of HMAF with gamma radiation. When drug treatment preceded irradiation, at least additive levels of apoptosis were observed in both androgen-responsive and androgen-independent cells. The combined treatment with ionizing radiation and HMAF reduced the radiation dose needed for the same level of clonogenic survival up to 2.5-fold. The potentiation of apoptosis and reduction in the clonogenic survival of tumor cells occurred at HMAF concentrations lower than that which reduced survival to 10% and at doses up to 6 Gy. No potentiation of apoptosis or clonogenic inhibition was noted in normal cells. These results suggest that the combination of HMAF with gamma radiation may have clinical utility for treatments of prostate cancer.