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, alpha-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.
Sotnichenko
A I
AI
Moscow Research Institute of Medical Ecology, Russia. sergsev@aha.ru
Severin
S E
SE
Posypanova
G A
GA
Feldman
N B
NB
Grigor'ev
M I
MI
Severin
E S
ES
Petrov
R V
RV
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000737:chemistry* / Q000633:toxicity; D012995:Solubility; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000737:chemistry*
D000970:Antineoplastic Agents; D000072317:Polychlorinated Dibenzodioxins; D000509:alpha-Fetoproteins