Role of the Ah locus in suppression of cytotoxic T lymphocyte activity by halogenated aromatic hydrocarbons (PCBs and TCDD): Structure-activity relationships and effects in C57Bl/6 mice congenic at the Ah locus

Journal Article · Sat Mar 31 23:00:00 EST 1990 · Fundamental and Applied Toxicology; (USA)

DOI:https://doi.org/10.1016/0272-0590(90)90257-K· OSTI ID:7011448

Kerkvliet, N I; Baecher-Steppan, L; Smith, B B; Youngberg, J A; Henderson, M C; Buhler, D R ^[1]

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1. Oregon State Univ., Corvallis (USA)

Previous studies have shown that the generation of cytotoxic T lymphocytes (CTL) following allogeneic tumor challenge is suppressed in Ah-responsive C57Bl/6 mice treated with a single oral dose of the toxic, Ah receptor-binding 3,4,5,3',4',5'-hexachlorobiphenyl (HxCB). The present studies have examined the specific role of the Ah receptor in this immunotoxic response by utilizing HxCB isomers of known, varied affinity for the Ah receptor as well as by comparing effects of high-affinity Ah receptor ligands (3,4,5,3',4',5'-HxCB and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)) on the CTL response of mice that differ only at the Ah locus, that is, Ah-responsive (Ahbb) and Ah-nonresponsive (Ahdd) congenic C57Bl/6 mice. Correlative changes in thymic weight, serum corticosterone (CS) levels, and spleen cellularity were also measured. The potency of HxCB congeners (3,4,5,3',4',5'-; 2,3,4,5,3',4'-; 2,4,5,2',4',5'-) and 2,3,7,8-TCDD to suppress the CTL response, to reduce spleen cellularity, to cause thymic atrophy, and to elevate serum CS levels was directly correlated with the binding affinity of the congener for the Ah receptor. Furthermore, these parameters of immunotoxicity in Ahdd C57Bl/6 mice were significantly more resistant to alterations induced by either 3,4,5,3',4',5'-HxCB or 2,3,7,8-TCDD as compared to Ahbb C57Bl/6 mice. These results strongly support an Ah receptor-dependent immunotoxic mechanism in suppression of the CTL response following acute exposure to halogenated aromatic hydrocarbons.

• OSTI ID: 7011448
• Journal Information: Fundamental and Applied Toxicology; (USA), Journal Name: Fundamental and Applied Toxicology; (USA) Vol. 14:3; ISSN 0272-0590; ISSN FAATD
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACUTE EXPOSURE
ANIMAL CELLS
ANIMALS
AROMATICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARCINOGENESIS
CELL PROLIFERATION
CHLORINATED AROMATIC HYDROCARBONS
CHROMIUM ISOTOPES
CONNECTIVE TISSUE CELLS
DIOXIN
ENZYMES
EXPERIMENTAL NEOPLASMS
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYDROXYLASES
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LYMPHATIC SYSTEM
LYMPHOCYTES
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MICE
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PATHOGENESIS
PROTEINS
RECEPTORS
RODENTS
SOMATIC CELLS
SPLEEN
STRUCTURE-ACTIVITY RELATIONSHIPS
THYMUS
TRACER TECHNIQUES
VERTEBRATES