Protection by WR-151327 against late-effect damage from fission-spectrum neutrons

The mutagenic and carcinogenic properties of fission-spectrum neutrons (KERMA-weighted mean energy of 0.85 MeV) from Argonne National Laboratory's JANUS reactor are substantially greater than those of low-LET radiation sources such as X-ray and 60Co photons. However, in contrast to the vast amount of work focused on chemical protection against damage induced by low-LET radiation, studies on the prevention of carcinogenic damage induced by fission neutrons have been limited. We have investigated the protective properties of the thiophosphorate compound S-3-(3-methylaminopropylamino)propylphosphorothioic acid (WR-151327) against carcinogenesis and life shortening in the B6CF1 hybrid mouse strain. Male and female mice, 200 of each sex per experimental group, were irradiated individually at 110 days of age. WR-151327 was administered intraperitoneally at a dose of 580 mg/kg 30 min prior to irradiation with a dose of 10 cGy. Animals were housed five to a cage; cage locations in holding rooms were controlled by computer and randomized. Mice were checked daily and all deceased animals were necropsied. A neutron dose of 10 cGy significantly altered the patterns of death of male and female animals compared to corresponding unirradiated control groups (logrank P values of 0.01 and 0.07, respectively). This was evidenced by a shortening of the life span due to tumor induction in the irradiated groups. WR-151327, when administered 30 min prior to irradiation, effectively protected both male and female animals from these effects. The life curves of irradiated male and female animals and those of corresponding unirradiated control groups were not significantly different (logrank P values of 0.63 and 0.25, respectively).