Ah locus: genetic differences in susceptibility to cataracts induced by acetaminophen

Abstract

The Ahb/Ahb homozygous and the Ahb/Ahd heterozygous inbred mouse strains from the (C57BL/6)(DBA/2)F1 X DBA/2 backcross are genetically responsive to 3-methylcholanthrene. They both also develop, within 6 hours after a large intraperitoneal dose of acetaminophen, an irreversible opacity in the anterior portion of the lens. Such cataract formation does not occur in similarly treated nonresponsive inbred strains or nonresponsive Ahd/Ahd individuals from the same backcross. Differences in acetaminophen metabolism and toxicity are associated with the Ah locus in the mouse, and differences in heritability at the Ah locus exist in the human. Our ophthalmologic findings may be important clinically to certain patients receiving either a single large overdose of this drug or high doses over a long period.