Microsomal Ferritin Iron Release in Relation to TCDD Toxicity

Abstract

Previous experiments have demonstrated that the hepatoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) involves synergism with iron. It has been postulated that it is storage iron that plays a role in toxic effects observed with TCDD poisoning. It was hypothesized that TCDD induction of the Ah gene locus in some way leads to mobilization of storage iron from the iron storage protein ferritin. Microsomal ferritin iron release was investigated in intact microsomes and in a reconstituted system. Evidence is presented which suggests that NADPH-cytochrome c (P450) reductase is capable of effecting the release of iron from flavin (FMN), and that at the same time, the reduced flavin thus generated is capable of effecting the release of iron from ferritin. While no direct evidence was obtained, the results do lend support to the hypothesis that TCDD toxicity could result from the mobilization of iron from ferritin by the TCDD induced microsomal electron transport system.