The immune basis of dosage-induced reversal of the rank-order of strain susceptibility to MCA.

Abstract

Even AHH-inducible mouse strains vary in their susceptibilities to MCA sarcomagenesis. Previous work showed that the rank-order of strain susceptibility depended upon the dosage of MCA; the strain most susceptible to a high dose became the least susceptible to a low one and vice versa. We now confirm our previous findings and test the hypothesis that the reversal, with dosage, of the rank-order of relative strain-susceptibility has an immunological basis. This was tested in two ways: by examining the effect of immunosuppression on strain-susceptibility to sarcomagenesis and by transplanting parental bone marrow into irradiated F1 hybrid to see if the relative MCA-susceptibility characteristics of the parental donors could be transferred. The results of both studies suggest that the rank-order-reversal phenomenon is caused, at least in part, by differences in the immunological reactivities of the strains. Inasmuch as immunosuppression inhibited the response of the C3 mice to a high dose of carcinogen, but facilitated carcinogenesis among the B6, the level of innate immune capacity most conducive to high-dose carcinogenesis is apparently intermediate between the levels of these two strains.