Possible reactive intermediates in the oxidative biotransformation of hexachlorobenzene

In this review the biotransformation of hexachlorobenzene is discussed, with special reference to the possible generation of reactive metabolites or intermediates during this process. Evidence is presented for the direct involvement of certain cytochrome P-450 isoenzymes in the major toxic effect of hexachlorobenzene, hepatic porphyria. The in vivo biotransformation is discussed and compared with in vitro experiments (microsomal and cell culture studies). The possible reactive metabolites and intermediates and their mechanisms of formation are presented. Special attention is directed to a very reactive metabolite, tetrachloro-1,4-benzoquinone, which has a high capacity to efficiently react with protein, thus possibly linking the oxidative biotransformation of hexachlorobenzene and the molecular mechanism of enzyme inactivation leading to hepatic porphyria.