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

• Published in: FEBS letters 1999-04, Vol.450 (1), p.49-51
• Main Authors: Sotnichenko, Alexander I., Severin, Sergey E., Posypanova, Galina A., Feldman, Natalya B., Grigor’ev, Michael I., Severin, Eugene S., Petrov, Rem V.
• Format: Article
• Language: English
• Subjects: 2,3,7,8-Tetrachlorodibenzo- p-dioxin; AFP, human α-fetoprotein; alpha-Fetoproteins - chemistry; Animals; Antineoplastic Agents - pharmacology; Complex; Embryotoxicity; FBS, fetal bovine serum; HPLC, high performance liquid chromatography; Humans; Injections, Intravenous; Mice; PBS, phosphate-buffered saline; Polychlorinated Dibenzodioxins - chemistry; Polychlorinated Dibenzodioxins - toxicity; Solubility; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; Toxicity; Tumor Cells, Cultured; α-Fetoprotein
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)00440-8

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, α-fetoprotein (AFP), have been studied. TCDD has been shown to form a stable complex with AFP in a 2:1 (TCDD:AFP) ratio. The apparent solubility of TCDD in water increases 10 5-fold after complex formation. The toxicity of the TCDD:AFP complex injected into mice by the intravenous route is comparable with that of free TCDD administered in oil solution per os. The complex 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 embryotoxic and teratogenic effects.