TY - JOUR
T1 - Halogenated aromatic hydrocarbon-induced suppression of the plaque-forming cell response in B6C3F1 splenocytes cultured with allogenic mouse serum
T2 - Ah receptor structure activity relationships
AU - Harper, N.
AU - Steinberg, M.
AU - Thomsen, J.
AU - Safe, S.
N1 - Funding Information:
The financial assistanceo f the National Institutes of Health (P42-ES04917)a nd the Texas Agricultural Experiment Station is gratefully acknowledgedS.. Safe is a Sid Kyle Professoro f Toxicology.
PY - 1995/5/23
Y1 - 1995/5/23
N2 - The immunsuppressive effects of halogenated aromatic hydrocarbons (HAHs) were investigated in B6C3F1 female mice and in mouse splenocytes cultured with allogenic mouse serum using the Mishell-Dutton model for in vitro immunization to trinitrophenyl-lipopolysaccharide (TNP-LPS). Exposure to 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 1,2,3,7,8-PeCDF, 1,3,6,8-tetrachlorodibenzofuran (TCDF), 3,3′,4,4′,5-pentachlorobiphenyl (pentaCB), or 3,3′,4,4′,5,5′-hexaCB resulted in a dose-dependent suppression of the splenic plaque-forming cell (PFC) response both in vivo and in vitro. The effective dose required to decrease 50% (ED50) of the response to 2,3,7,8-TCDD, 2,3,4,7,8-PeCDF, 1,2,3,7,8-PeCDF, 1,3,6,8-TCDF, 3,3′,4,4′,5-pentaCB, or 3,3′,4,4′,5,5′-hexaCB in vivo was 14.1, 5.5, 1695, 34800, 21, and 19 nmol/kg, respectively, and in vitro was 7.0, 10.6, 149, 2325, 9.1 and 9.1 nM, respectively. There was an excellent rank order and linear correlation between the in vivo versus in vitro activities for these HAHs (r < 0.99) and the relative immunosuppressive potencies of these compounds paralleled their binding affinities for the aryl hydrocarbon (Ah) receptor. These results show that splenocytes cultured with allogenic mouse serum is an Ah-responsive in vitro assay which can be used for quantitating the immunosup-pressive effects of HAHS.
AB - The immunsuppressive effects of halogenated aromatic hydrocarbons (HAHs) were investigated in B6C3F1 female mice and in mouse splenocytes cultured with allogenic mouse serum using the Mishell-Dutton model for in vitro immunization to trinitrophenyl-lipopolysaccharide (TNP-LPS). Exposure to 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 1,2,3,7,8-PeCDF, 1,3,6,8-tetrachlorodibenzofuran (TCDF), 3,3′,4,4′,5-pentachlorobiphenyl (pentaCB), or 3,3′,4,4′,5,5′-hexaCB resulted in a dose-dependent suppression of the splenic plaque-forming cell (PFC) response both in vivo and in vitro. The effective dose required to decrease 50% (ED50) of the response to 2,3,7,8-TCDD, 2,3,4,7,8-PeCDF, 1,2,3,7,8-PeCDF, 1,3,6,8-TCDF, 3,3′,4,4′,5-pentaCB, or 3,3′,4,4′,5,5′-hexaCB in vivo was 14.1, 5.5, 1695, 34800, 21, and 19 nmol/kg, respectively, and in vitro was 7.0, 10.6, 149, 2325, 9.1 and 9.1 nM, respectively. There was an excellent rank order and linear correlation between the in vivo versus in vitro activities for these HAHs (r < 0.99) and the relative immunosuppressive potencies of these compounds paralleled their binding affinities for the aryl hydrocarbon (Ah) receptor. These results show that splenocytes cultured with allogenic mouse serum is an Ah-responsive in vitro assay which can be used for quantitating the immunosup-pressive effects of HAHS.
KW - Ah receptor agonists
KW - Allogenic mouse serum
KW - Halogenated aromatic hydrocarbons
KW - Immunotoxicity
KW - Splenocytes
UR - http://www.scopus.com/inward/record.url?scp=0029002807&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029002807&partnerID=8YFLogxK
U2 - 10.1016/0300-483X(95)03064-M
DO - 10.1016/0300-483X(95)03064-M
M3 - Article
C2 - 7610466
AN - SCOPUS:0029002807
SN - 0300-483X
VL - 99
SP - 199
EP - 206
JO - Toxicology
JF - Toxicology
IS - 3
ER -