The ability of graded single doses of WR-2721 to raise the x-ray <tex-math>${\rm LD}_{50(30)}$</tex-math> of adult females of four inbred mouse strains (A/J, BALB/cJ, C57BL/6J, and DBA/2J) has been studied. Protective responses expressed as a dose reduction factor or DRF (<tex-math>${\rm LD}_{50(30)}$</tex-math> <tex-math>$\text{treated}/{\rm LD}_{50(30)}$</tex-math> untreated) show significant strain differences. These differences are not correlated with differences in body weight (which are used to calculate the drug dose per animal) or with differences in inherent resistance (i.e., strains with low untreated <tex-math>${\rm LD}_{50(30)}$</tex-math> values do not show higher or lower DRF values than strains with high untreated <tex-math>${\rm LD}_{50(30)}$</tex-math> values). However, the differences do correlate with differences in tolerance to the toxic side effects of the drug. Both radiosensitive (A/J) and radioresistant (DBA/2J) strains that are sensitive to the toxic side effects of the drug show a rapid increase in the DRF as a function of drug dose, whereas the radiosensitive (BALB/cJ) and radioresistant (C57BL/6J) strains that are resistant to the toxic side effects of the drug show a less rapid increase. It has been shown that the plasma acid phosphatase activity and the toxicity of this drug are inversely correlated in these strains. Since removal of the phosphate in the plasma would reduce cellular permeability of the drug, the association of high acid phosphatase activity, low toxicity, and relatively low protection is not unexpected.

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