INFLUENCE OF HEREDITY ON HUMAN SENSITIVITY TO ENVIRONMENTAL CHEMICALS

Hereditary peculiarities in individual responses to environmental chem icals are a common occurrence in human populations. Genetic variation in glutathione S-transferase, CYP1A2, N-acetyltransferase, and paraoxo nase exemplify the relationship of metabolic variation to individual s usceptibility cancer and other toxicants of environmental origin. Heri table receptor protein variants, a subset of proteins of enormous phar macogenetic potential that have not thus for been extensively explored from the pharmacogenetic standpoint, are also considered. Examples of interest that ore considered include receptor variants associated wit h retinoic acid resistance in acute promyelocytic leukemia, with parad oxical responses to antiandrogens in prostrate cancer, and with retini tis pigmentosa. Additional heritable protein variants of pharmacogenet ic interest that result in antibiotic-induced deafness, glucocorticoid -remediable aldosteronism and hypertension, the long-QT syndrome, and beryllium-induced lung disease are also discussed. These traits demons trate how knowledge of the molecular basis and mechanism of the varian t response may contribute to its prevention in sensitive persons as we ll as to improved therapy for genetically conditioned disorders that a rise from environmental chemicals. (C) 1995 Wiley-Liss, Inc.