Increased formation of DNA adducts in cultured fibroblasts of patients with aplastic anemia after in vitro incubation with benzo(a)pyrene.

In inbred mice strain DBA/2, genetically controlled differences in aryl hydrocarbon hydroxylase (AHH) activity have been demonstrated that predispose to aplastic anemia. To test the hypothesis of a similar mechanism in humans, we studied the formation of benzo(a)pyrene DNA adducts and water-soluble metabolites in skin fibroblasts from eight patients with aplastic anemia and eight normal controls. The ratio of water-soluble metabolites and DNA adducts was 46.5 +/- 16.6 in patients and was significantly lower as compared to 82.9 +/- 38.5 in controls (P less than 0.05). We conclude that increased formation of genotoxic intermediates may be a pathogenetic mechanism in some patients with aplastic anemia.