Association between susceptibility to dibenzanthracene‐induced fibrosarcoma formation and the Ah locus

The relationship between the Ah locus and the induction of subcutaneous fibrosarcomas by dibenz[a,h]anthracene and dibenz[a,c]anthracene was investigated in C57BL/6J ( Ah b /Ah b ), (C57BL/6J)(DBA/2J)F 1 ( Ah b /Ah d ) and ( Ah d /Ah d ) mice. Ah b /Ah b and Ah b /Ah d mice have the high‐affinity Ah receptor and therefore the polycyclic hydrocarbon induction of aryl hydrocarbon hydroxylase activity (cytochrome P 1 ‐450) proceeds with ease; Ah d /Ah d mice have the poor‐affinity Ah receptor and this induction process proceeds more poorly, by a factor of at least 10‐fold. Dibenz[a,c]anthracene proved to be a relatively weak carcinogen, producing less than 3% tumor incidence at doses up to 300 μg per mouse. In contrast, dibenz‐[a,h]anthracene caused an almost 50% tumor incidence in Ah b /Ah b and Ah b /Ah d mice, while causing ∼2% tumor incidence in Ah d /Ah d mice. Both isomers bind avidly to the cytosolic Ah receptor, and both chemicals induce aryl hydrocarbon hydroxylase activity in Ah b /Ah b and Ah d /Ah d animals. Among progeny of the (C57BL/6J) (DBA/2J) F 1 × DBA/2J backcross, 63 of 100 Ah b /Ah d mice and none of 75 Ah d /Ah d mice developed tumors. These data demonstrate a strict correlation between susceptibility to dibenz[a,h]anthracene‐induced subcutaneous tumors and expression of the Ah b allele, i.e. presence of the high‐affinity Ah receptor and therefore readily inducible P 1 ‐450.