Pharmacogenetic studies on the drug-related lupus syndrome. differences in antinuclear antibody development and drug-induced DNA damage in rapid and slow acetylator animal models

摘要

Pharmacogenetic study of an inbred mouse model system derived from A/J (slow acetylator) and C57BL/6J (rapid acetylator) parental strains shows that spontaneous occurrence of antinuclear antibodies is associated with the slow acetylator phenotype although the development of spontaneous and procainamide-induced antinuclear antibodies is a dissociable process. In another study using primary cultures of intact hepatocytes obtained from slow and rapid acetylator rabbits, observations indicate that the amount of DNA damage induced by exposure to hydrazine and arylamine containing foreign compounds depends on the concentration of the foreign compound used as well as on the acetylator phenotype. Exposure to hydralazine induced greater DNA damage in slow acetylator hepatocytes whereas exposure to the arylamine carcinogen, 2-aminofluorene, induced greater DNA damage in rapid acetylator hepatocytes.