SUMMARY

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocar-bons (a) produce a similar pattern of toxic responses; (b) induce a battery of enzymes, including aryl hydrocarbon hydroxylase (AHH) activity; and (c) bind reversibly and with a high affinity to a cytosol protein that is the receptor for this enzyme induction response. To test the hypothesis that the toxic effects produced by these compounds are mediated by their binding to the induction receptor, we examined the genetic segregation of two toxic responses, with the Ah locus, which determines this receptor. The dose-response relationship for thymic atrophy produced by TCDD was examined in C57BL/6J mice, which have a high affinity receptor and are sensitive to enzyme induction, DBA/2J mice, which have a lower affinity receptor and are less sensitive to induction of AHH activity, and hybrid B6D2F,/J mice. C57BL/6J mice were approximately 10-fold more sensitive to thymic involution than DBA/2J mice and the hybrid BGD2F,/J were intermediate between the two parental strains. The progeny of a B6D2F,/J x DBA/2J mating were phenotyped (as Aa or aa), and the mice heterozygous for the high affinity receptor were more sensitive to thymic atrophy. The capacity of other halogenated aromatic hydrocar