Radioprotective effect of amifostine on cells from cancer prone patients and healthy individuals studied by the G2 and PCC assays.
OBJECTIVE
To investigate whether amifostine is effective at reducing the yield of chromatid breaks when present during G(2)-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.


METHODS
G(2) 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 gamma-irradiation in G(2) phase was obtained at the subsequent metaphase using the G(2) assay. For scoring chromatid damage directly in G(2) or G(0) 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 G(2) 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 G(2) or G(0) phase using premature chromosome condensation, the presence of amifostine did not affect the yields obtained.


CONCLUSIONS
Amifostine reduces the mean yield of chromatid breaks in normal cells and in cells from cancer prone patients when present during G(2) 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.
Manola
K N
KN
Laboratory of Health Physics & Environmental Hygiene NCSR 'Demokritos', Agia Paraskevi Athens Greece.
Terzoudi
G I
GI
Dardoufas
C E
CE
Malik
S I
SI
Pantelias
G E
GE
D004999:Amifostine / Q000008:administration & dosage*; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000187:drug effects*; D020732:Cytogenetic Analysis; D016195:G2 Phase / Q000187:drug effects* / Q000528:radiation effects*; D020022:Genetic Predisposition to Disease / Q000517:prevention & control*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology*; D011230:Precancerous Conditions; D011835:Radiation Protection / Q000379:methods; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D012016:Reference Values
D011837:Radiation-Protective Agents; D004999:Amifostine