Dioxin induction

Fowler BA, Hook GER, Lucier GW. 1977. Tetrachlorodibenzo-p-dioxin induction of renal microsomal enzyme systems Ultrastructural effects on pars recta (S3) proximal tubule cells of the rat kidney. J Pharmacol Exp Ther 203 712-721. 

Lee CA, Lawrence BP, Kerkvliet NI, Rifkind AB. 1998. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin induction of cytochrome P450-dependent arachidonic acid metabolism in mouse liver microsomes ... 

Xu L, Li AP, Kaminski DL, Ruh MF. 2,3,7,8 Tetrachlorodibenzo-p-dioxin induction of cytochrome P4501A in cultured rat and human hepatocytes. Chem Biol Interac 2000 124 173-89. 

Guiney, P.D., R.M. Smolowitz, R.E. Peterson and J.J. Stegeman. Correlation of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction of cytochrome P4501A in vascular endothelium with toxicity in early life stages of lake trout. Toxicol. Appl. Pharmacol. 143 256-273, 1997. 

Lu, F., Zahid, M., Saeed, M., Cavalieri, E. L., and Rogan, E. G. (2007) Estrogen metabolism and formation of estrogen-DNA adducts in estradiol-treated MCF-10F cells. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction and catechol-O-methyltransferase inhibition. J. Steroid Biochem. Mol. Biol. 105, 150-158. 

Taylor RT, Wang F, Hsu EL, Hankinson O (2009) Roles of coactivator proteins in dioxin induction of CYPl Al and CYPIBI in human breast cancer cells. Toxicol Sci 107 1-8... 

There is increasing interest in the relationship of the HS response to environmental toxicology. As induction of the HS response portends resistance to otherwise lethal stresses, many environmental hazards have the potential for inducing the HS response (Finnell et al., 1992). Activity of the dioxin receptor is affected by HS proteins (Nemoto et al., 1990 Pongratz et al., 1992) and it is likely that the HS... 

Toxic equivalency factors (TEFs) are estimated relative to 2,3,7,8-TCDD, which is assigned a value of 1. They are measures of the toxicity of individual compounds relative to that of 2,3,7,8-TCDD. A variety of toxic indices, measured in vivo or in vitro, have been used to estimate TEFs, including reproductive effects (e.g., embryo toxicity in birds), immunotoxicity, and effects on organ weights. The degree of induction of P450 lAl is another measure from which estimations of TEF values have been made. The usual approach is to compare a dose-response curve for a test compound with that of the reference compound, 2,3,7,8-TCDD, and thereby establish the concentrations (or doses) that are required to elicit a standard response. The ratio of concentration of 2,3,7,8-TCDD to concentration of test chemical when both compounds produce the same degree of response is the TEF. Once determined, a TEF can be used to convert a concentration of a dioxin-like chemical found in an environmental sample to a toxic equivalent (TEQ). 

PCDDs and PCDEs, together with coplanar PCBs, can express Ah-receptor-mediated toxicity. TCDD (dioxin) is used as a reference compound in the determination of TEFs, which can be used to estimate TEQs (toxic equivalents) for residues of PHAHs found in wildlife samples. Biomarker assays for Ah-receptor-mediated toxicity have been based on the induction of P450 lAl. TEQs measured in field samples have sometimes been related to toxic effects upon individuals and associated ecological effects (e.g., reproductive success). 

Coplanar PCBs, PCDDs, and PCDFs express Ah-receptor-mediated toxicity (Chapter 6, Section 6.2.4). Binding to the receptor leads to induction of cytochrome P4501 and a number of associated toxic effects. Again, toxic effects are related to the extent of binding to this receptor and appear to be additive, even with complex mixtures of planar polychlorinated compounds. Induction of P4501A1/2 has been widely used as the basis of a biomarker assay. Residue data can be used to estimate TEQs for dioxin (see Chapter 7, Section 7.2.4). 

Owing to the fact that ethyl ethers are especially effective substrates for CYP1A1 [184], the probe possesses an ethyl group on the phenolic oxygen of the trimethyl lock. In vitro, fluorescence was manifested by CYP1A1 isozyme with Kcat/KM 8.8 x 103 M-1s 1 and KM 0.09 pM. In cellulo, the probe revealed the induction of cytochrome P450 activity by the carcinogen 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD), and its repression by the chemoprotectant resveratrol. 

Certain structural features have been identified as being associated with high degrees of toxicity, AHH induction and receptor binding for the dibenzo-p-dioxins and related compounds (Poland and Knutson 1982). These are as follows ... 

Cheney, B. V. 1982. Structural Factors Affecting Aryl Hydrocarbon Hydroxylase Induction of Dibenzo-p-Dioxins and Dibenzofurans. Int. J. Quant. Chem. 21,445. 

Beebe, L.E., L.W. Fomwald, and L.M. Anderson. 1992. Effect of a single oral dose of 2,3,7,8-tetrachlorod-ibenzo-p-dioxin (TCDD) on hepatic and extrahepatic cytochrome P-450 IA induction in the Swiss mouse. Chemosphere 25 1141-1145. 

Van der Weiden, M.E.J., R. Bleumink, W. Seinen, and M. Van den Berg. 1994. Concurrence of P450 1A induction and toxic effects in the mirror carp (Cyprinus carpio), after administration of a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Aquat. Toxicol. 29 147-162. 

Brunstrom, B., M. Engwall, K. Hjelm, L. Lindqvist, and Y. Zebuhr. 1995. EROD induction in cultured chick embryo liver a sensitive bioassay for dioxin-like environmental pollutants. Environ. Toxicol. Chem. 14 837-852. 

Camacho, I., Nagarkatti, M., and Nagarkatti, P., Evidence for induction of apoptosis in T cells from murine fetal thymus following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin, Toxicol. Sci., 78, 96, 2004. 

Munzel PA, Schmohl S, Heel H, Kalberer K, Bock-Hennig BS, Bock KW (1999) Induction of human UDP glucuronosyltransferases (UGT1A6, UGT1A9, and UGT2B7) by t-butylhydroquinone and 2,3,7,8-tetrachlorodibenzo-p-dioxin in Caco-2 ceUs. Drug Metab Dispos 27(5) 569-573... 

For halogenated aromatic hydrocarbons like polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) the binding to the aryl hydrocarbon (Ah) receptor regulates their toxicity [89]. The Ah receptor controls the induction of one of the cytochrome P450 enzymes in the liver. Toxic responses such as thymic atrophy, iveight loss, immu-notoxicity and acute lethality are associated ivith the relative affinity of PCBs, PCDFs and PCDDs for the Ah receptor [89]. The quantitative structure-activity relationship (QSAR) models predicting the affinity of the halogenated aromatic hydrocarbons ivith the Ah receptor describe the electron acceptor capability as well as the hydrophobicity and polarizability of the chemicals [89[. 

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