Considerations on Genetic and Environmental Factors That Contribute to Resistance or Sensitivity of Mammals Including Humans to Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds

Non-Ahr Gene Susceptibility Loci for Porphyria and Liver Injury Induced by the Interaction of ‘Dioxin’ with Iron Overload in Mice

“…There are at least three QTLs on chromosomes 1, 11, and 14, and probably one on chromosome 9, besides Ahr, that are responsible for the differences in susceptibility between DBA/2 mice and the C57BL/6J and SWR strains. Thus, as far as liver injury is concerned, the view that resistance to dioxin in mice is completely dominated by the Ahr d allele is misleading, as has been argued previously (Greig et al, 1984;Pohjanvirta and Tuomisto, 1994;Geyer et al, 1997). It seems likely that at least one QTL will be linked with liver iron mobilization and metabolism and that interactions with expressions mediated by the AHR lead to depression of UROD activity, porphyria, and some aspects of hepatic injury, which can result in elevated plasma ALT and AST levels.…”

“…The Ahr null mouse seems to be intractably resistant to environmental chemicals of the dioxin type (Fernandez-Salguero et al, 1996)). On the other hand, there is considerable tissue and species variability in response to dioxin that cannot be ascribed simply to polymorphisms of the Ahr gene (Pohjanvirta and Tuomisto, 1994;Geyer et al, 1997). This suggests that other modulating genes have profound effects on AHR-mediated toxicity.…”

The AH Receptor of the Most Dioxin-Sensitive Species, Guinea Pig, Is Highly Homologous to the Human AH Receptor

“…However, while the Guinea pig exhibits extreme susceptibility to the acute toxicity of TCDD, there are no reported cases of acute mortality among people exposed to dioxins. Data from occupational and accidental exposures also imply that humans are more resistant to acute lethality of dioxins than Guinea pigs (29). For example, in the industrial accident of Seveso in 1976, TCDD concentrations of up to 56,000 ng/kg in fat were recorded (30).…”

An Assessment of Mutagenic Effect of 3, 3', 4, 4', 5 Pentachlorobiphenyl (PCB126) in Muta Mouse Fetuses

“…Another study of chickens noted that when 10 or 20 ppm of PCB compounds (Aroclors 1232, 1242, 1248) were fed to a White Leghorn, hatchability (%) varied from 78 to 5, as compared with 90 for the controls [20], and the 50% mortality rate of PCB 126, 77, and 105 were 0.6, 8.8, and 5592 g/ kg per egg, respectively [30]. It might be that PCB congeners vary in their teratogenic potential as reported by Ulbrich and Stahlmann [35], according to sensitivity differences among animal species and PCB strains as reported by Geyer et al [8]. It might also be the number or expressions of the receptor for PCB, such as aryl hydrocarbon receptor (AhR) which mediates the toxicity of dioxin-like compounds, differs, as reported by Hassoun et al [13] and Brunstrom et al [2].…”