Water-soluble 2,3,7,8-tetrachlorodibenzo-p-dioxin complex with human alpha-fetoprotein: properties, toxicity in vivo and antitumor activity in vitro

The conditions for the formation of a non-covalent complex between 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and the human transport fetal protein, a lpha-fetoprotein (AFP), have been studied. TCDD has been shown to form a st able complex with AFP in a 2:1 (TCDD:AFP) ratio. The apparent solubility of TCDD in mater increases 10(5)-fold after complex formation. The toxicity o f the TCDD:AFP complex injected into mice by the intravenous route is compa rable with that of free TCDD administered in oil solution per os, The compl ex manifests very much higher toxicity (200-1400 times) against human tumor cells (CEM, MCF-7, HepG2) in vitro and surpasses TCDD in selectivity. AFP may facilitate TCDD transport in embryonic tissues and enhance its embryoto xic and teratogenic effects. (C) 1999 Federation of European Biochemical So cieties.