Radioprotective effect of amifostine on cells from cancer prone patients and healthy individuals studied by the G₂ and PCC assays

Abstract

Purpose: To investigate whether amifostine is effective at reducing the yield of chromatid breaks when present during G₂‐phase irradiation of human normal cells and cells from cancer prone patients, as well as to study the mechanisms underlying the radioprotective effect of amifostine.

Materials and methods: G₂ chromosomal radiosensitivity in the presence or absence of amifostine was studied in healthy donors, cancer patients, ataxia‐telangietasia (A‐T) patients and five human lymphoblastoid cell lines with genes predisposing to cancer. The yield of chromatid breaks following γ‐irradiation in G₂ phase was obtained at the subsequent metaphase using the G₂ assay. For scoring chromatid damage directly in G₂ or G₀ phase, premature chromosome condensation was used.

Results: When amifostine was present during irradiation, the mean yield of radiation‐induced chromatid breaks as visualized by the G₂ assay was significantly reduced in healthy donors (t‐test, p=0.001), in cells from cancer patients (p=0.001) and in cell lines from patients with genes predisposing to cancer (p=0.01) except ATM^−/− (0.1<p<0.2). However, when chromatid breaks were scored directly in G₂ or G₀ phase using premature chromosome condensation, the presence of amifostine did not affect the yields obtained.

Conclusion: Amifostine reduces the mean yield of chromatid breaks in normal cells and in cells from cancer prone patients when present during G₂ irradiation. Although the precise mechanisms of radioprotection caused by amifostine remain unclear, the results obtained using premature chromosome condensation reveal that amifostine does not act on cells only as a free radical scavenger and as a repair enhancer of DNA damage.