Species, strain and sex differences in susceptibility to gamma radiation combined with diethylnitrosamine

Our previous data suggested that in Sprague-Dawley (SD) rats, a short-term in vivo radiation carcinogenesis model can be established using glutathione S-transferase placental form (GST-P) positive hepatic foci induced by diethylnitrosamine (DEN) after gamma radiation. In the present study, differences between species, strain and sexes in susceptibility to radiation or radiation combined with DEN were examined. Newborn Fischer 344 (F344) and SD rats, and N:GP(S) mice were irradiated with whole body single 3Gy of gamma rays with or without intraperitoneally-injected DEN (15 mg/kg body weight) within 1 h of irradiation. Three weeks later, 0.05% phenobarbital was given in drinking water as a promoter, and at week 21 after birth, all animals were sacrificed. In both the radiation alone and radiation combined with DEN groups, F344 rats were more susceptible than SD rats to the induction of GST-P⁺ foci. In F344 rats, no significant difference in foci induction was seen between the sexes in both radiation alone and radiation combined with DEN groups, but in SD rats, female rats were more susceptible than males. In the case of mice, lung tumor incidence was examined, and in the radiation alone group, no differences between the sexes were seen; in the radiation combined with DEN group, however, females were more susceptible than males. These results suggested that susceptibility to radiation carcinogenesis could be potentiated by chemical carcinogens and showed wide variation between species, strains and sexes, of experimental animals.