Immunosuppressive activities of polychlorinated dibenzofuran congeners: Quantitative structure-activity relationships and interactive effects

Immunological Effects of Chlorinated Dibenzo-p-Dioxins

“…Two lines of evidence support this conclusion: comparative studies using PCDD, PCDF, and PCB congeners show that potency to cause immune suppression correlates with the binding affinity for the AhR (25)(26)(27)(28)(29); and studies using mice with a defined Ah genotype show that mice with high affinity AhR (e.g., Ahbb C57BI/6 mice) are more sensitive to immune suppression by these compounds than mice with lower affinity AhR (e.g., Ahdd DBA/2 mice or Ahdd congenic C57BI/6 mice) (8,25,26,29). AhR-dependent responses include suppression of the T-cell-dependent antibody response to SRBC (8,(25)(26)(27)(28)30,31), suppression of the T-cell-independent antibody response to trinitrophenyl-lipopolysaccharide (8), suppression of the cytotoxic T lymphocyte (CTL) response to allogeneic tumor cells (29,32) bone marrow toxicity (33), and suppression of the cytotoxic responses of activated neutrophils (34 however, the specific cellular defects induced by TCDD have not been fully elucidated despite considerable research. One of the problems has been a difficulty in demonstrating direct effects of TCDD on in vitro responses of lymphoid cells (35,36).…”

Characterization of an aryl hydrocarbon receptor from a cetacean : an approach for assessing contaminant susceptibility in protected species

“…The severity of the suppressive effect correlated with the specific binding affinity of the HAR to the ARR, supporting an AHR mediated mechanism. Such a relationship has been shown for various PCB congeners ) and polychlorinated dibenzofurans (Davis & Safe, 1988;Dickerson et al, 1990). That the AHR antagonist alpha-napthoflavone can abrogate both CYPIA enzyme activity and suppression of hemolytic plaques formed is consistent with an AHR-mediated mechanism (Blank et al, 1987).…”

Opposite Effects of 2,2′,4,4′,5,5′-Hexachlorobiphenyl and 2,3,7,8-Tetrachlorodibenzo-p-dioxin on the Antibody Response to Sheep Erythrocytes in Mice

“…One of the most sensitive toxic endpoints of HAH exposure in mice is suppression of the primary antibody response to sheep red blood cells (SRBCs), as determined by the splenic plaqueforming cell (PFC) response, following a single exposure to TCDD. The reproducibility and sensitivity of this T lymphocyte-dependent antibody response to suppression by TCDD have been corroborated by a number of laboratories that have demonstrated an ED50 of approximately 0.7 fj,g TCDD/ kg (Vecchi et al, 1980;Davis and Safe, 1988;Kerkvliet et al, 1990;Smialowicz et al, 1994).…”