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Amifostine and Tissue Toxicity in Gamma Ray and Neutron Exposed Mice

Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine

, , , , , & , PhD show all
Pages 623-634 | Received 07 Dec 2007, Accepted 21 May 2008, Published online: 03 Jul 2009
 

Abstract

Purpose: To determine the effects of Amifostine or WR-151327 on the incidence of lethal and non-lethal toxicities in a large cohort of mice exposed to γ-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-151327, 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.

Acronyms
HPRT=

hypoxanthine-guanine phosphoribosyl transferase

OR=

odds ratio (odds ratio in control is always set on 1)

PC=

non-tumor pathological changes

RBE=

relative biological effectiveness

WBI=

whole body irradiation

WR1065=

N-[2-mercaptoethyl]-1,3-diaminopropane; active form of Amifostine

WR151327=

S-2-[3-methylaminopropylamino] propylphosphorothioic acid

WR2721=

S-2-[3-aminopropylamino] ethylphosphorothioic acid; or Amifostine

Acronyms
HPRT=

hypoxanthine-guanine phosphoribosyl transferase

OR=

odds ratio (odds ratio in control is always set on 1)

PC=

non-tumor pathological changes

RBE=

relative biological effectiveness

WBI=

whole body irradiation

WR1065=

N-[2-mercaptoethyl]-1,3-diaminopropane; active form of Amifostine

WR151327=

S-2-[3-methylaminopropylamino] propylphosphorothioic acid

WR2721=

S-2-[3-aminopropylamino] ethylphosphorothioic acid; or Amifostine

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