Factors affecting the toxicity of dioxin-like toxicants: a molecular approach to risk assessment of dioxins.
The numerous toxic responses of dioxin-like compounds are mediated by the intracellular Ah (aryl hydrocarbon) receptor. It has been suggested that the regulation of dioxins and similar substances could be placed on a molecular foundation by considering the proportion of Ah-receptor sites occupied by toxicant molecules. The present work has shown that the following formation not yet available would be needed in order to develop this approach: correlation between dioxin exposure and human tissue levels; accurate determination of the association constants for human Ah-receptor with toxicant, and for human receptor-ligand complex with DNA; and knowledge of the intracellular concentrations of both receptor binding sites and DNA binding sites. Furthermore, since not all dioxin-like substances behave identically, this information would need to be gathered for a wide variety of substances.
Brown
M M
MM
Department of Chemistry and Biochemistry, University of Guelph, Ontario, Canada.
McCready
T L
TL
Bunce
N J
NJ
D000818:Animals; D001665:Binding Sites; D004147:Dioxins / Q000633:toxicity*; D006801:Humans; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism; D012307:Risk Factors
D004147:Dioxins; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug