Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine.
OBJECTIVE
To determine the effects of Amifostine or WR-151,327 on the incidence of lethal and non-lethal toxicities in a large cohort of mice exposed to gamma-ray or fission-spectrum neutron radiation.


METHODS
To analyze data from 4000 B6CF1 mice which received a single whole body irradiation (WBI) with 206 cGy or 417 cGy cobalt-60 gamma rays or 10 cGy or 40 cGy of fission-spectrum neutrons (average energy 0.85 MeV) produced by the Janus reactor at Argonne National Laboratory. In the neutron cohort, Amifostine, WR-151,327, saline or nothing was injected once, intraperitoneally, 30 minutes before irradiation. In the cobalt-60 cohort, WR-151327 was omitted from the same protocol. At the time of natural death, tissue toxicities found in these mice were recorded, and these records were analyzed. While all previous studies focused on the modulation of life shortening effects of WBI by Amifostine, in this study we calculated changes in the frequencies of 59 tissue toxicities and changes in the total number of toxicities per animal.


RESULTS
Amifostine protected against specific non-tumor pathological complications (67% of the non-tumor toxicities induced by gamma irradiation, 31% of the neutron induced specific toxicities), as well as specific tumors (56% of the tumor toxicities induced by gamma irradiation, 25% of the neutron induced tumors). Amifostine also reduced the total number of toxicities per animal for both genders in the gamma ray exposed mice and in males in the neutron exposed mice.


CONCLUSIONS
Amifostine was protective against many, but not all, tissue toxicities caused by WBI gamma and neutron irradiation.
Paunesku
David
D
Department of Radiation Oncology, University of Chicago, Chicago, Illinois, USA.
Paunesku
Tatjana
T
Wahl
Andrew
A
Kataoka
Yasushi
Y
Murley
Jeffrey
J
Grdina
David J
DJ
Woloschak
Gayle E
GE
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009502:Neutrons / Q000009:adverse effects*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014916:Whole-Body Irradiation
D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; C048392:WR 151327; D004999:Amifostine