Genetic differences in drug metabolism associated with ocular toxicity.
The tissue localization and subcellular distribution of drug-metabolizing enzymes in the eye are described. With the use of inbred strains of mice, the [Ah] complex is shown to be an important experimental system for probing genetic differences in drug metabolism and related drug toxicities. Although the genetic system described in detail here involves mice, there is ample evidence that the same system operates in man. Genetic differences in acetaminophen- and naphthalene-induced cataract formation and and other ocular degeneration are shown to be related to the [Ah] complex. Because this toxicity appears similar to senile cataracts, we propose that certain types of drug-induced cataracts might exist among clinical populations of senile cataracts but that any cause-and-effect relationship would be very difficult to determine because of underlying interindividual differences in genetic predisposition. It is therefore suggested that genetic differences in drug metabolism be an important consideration in the clinical assessment of ocular toxicity caused by drugs and other environmental pollutants.
D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002386:Cataract / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005123:Eye / Q000648:ultrastructure; D005128:Eye Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009281:Naphthalenes / Q000633:toxicity; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010641:Phenotype; D013347:Subcellular Fractions / Q000201:enzymology
D009281:Naphthalenes; D004364:Pharmaceutical Preparations; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases