Amifostine has an inhibitory effect on the radiation-induced p53-branched cascade in the immature mouse ovary.
The organic thiophosphate, amifostine, is a promising pharmacological compound showing selective protection in many tissues against the toxic side-effects of radiation and cytotoxic drugs. The aim of the present study was to assess the radioprotective effects of amifostine on ovarian follicles. Three-week-old female mice, with or without pretreatment with amifostine, were irradiated with 6.42 Gy of gamma-ray. Reduced proliferation of granulosa cells was verified with BrdU staining and the incidences of follicular degeneration increased in ovarian follicles in the gamma-ray-irradiated mice compared to that of the control or amifostine-treated group. Biochemical changes caused by gamma-irradiation provoked a rise of p53 and Bax protein and a decline of the inactive form in caspase-3 and PARP protein. Caspase-3 and PARP cleaved into active peptides during apoptosis. This process was confirmed by the result of this study, which was that the amount of the stable form decreased immediately after irradiation. In the amifostine treatment group before irradiation, the increased rate of p53 and Bax was suppressed, particularly in the LDs-treated group. The relationship between PARP and caspase-3 levels showed the effect of amifostine exposure before irradiation. In conclusion, amifostine had an inhibitory effect on ovarian programmed cell death induced by gamma-ray, affecting the expression of apoptotic signaling molecules and the level of proliferation of the granulosa cells.
Yoon
Yong-Dal
YD
Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Korea.
Kim
Ji Hyang
JH
Lee
Kyoung Hee
KH
Kim
Jin Kyu
JK
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001973:Bromodeoxyuridine; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008813:Mice, Inbred ICR; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012741:Sexual Maturation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000528:radiation effects; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D001973:Bromodeoxyuridine; D004999:Amifostine