Immunological and neurobiochemical alterations induced by repeated oral exposure of phenol in mice.
Phenol, a major metabolite of benzene, is a potentially immunotoxic and neurotoxic substance of environmental significance. Male CD-1 mice were continuously exposed to 0, 4.7, 19.5, and 95.2 mg phenol/l in drinking water for 4 weeks. Various immune functions were evaluated and levels of selected neurotransmitters and metabolites measured in discrete brain regions. The doses of phenol did not produce any overt clinical signs of toxicity; peripheral red blood cell counts and hematocrits decreased. A dose of 95.2 mg/l suppressed the stimulation of cultured splenic lymphocytes by lipopolysaccharide, pokeweed mitogen, and phytohemagglutinin and the response in mixed lymphocyte cultures. The two high doses suppressed antibody production response to the T cell-dependent antigen (sheep erythrocytes), as determined by plaque-forming cells, and serum antibody levels. Mice treated with phenol had lower levels of neurotransmitters in several brain regions. In the hypothalamus, a major norepinephrine-containing compartment, the concentrations of norepinephrine significantly decreased by 29 and 40% in groups dosed with 19.5 and 95.2 mg/l, while dopamine concentrations decreased in the corpus striatum by 21, 26, and 35% at 4.7, 19.5 and 95.2 mg/l, respectively. Phenol also decreased 5-hydroxytryptamine in the hypothalamus, medulla oblongata, midbrain and corpus striatum. Levels of monoamine metabolites decreased in the hypothalamus (5-hydroxyindoleacetic acid), midbrain (vanillylmandelic acid), corpus striatum (vanillylmandelic acid and dihydroxyphenylacetic acid), cortex (vanillylmandelic acid), and cerebellum (dihydroxyphenylacetic acid).
Hsieh
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Department of Biology, Utah State University, Logan 84322-5600.
Sharma
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Parker
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Coulombe
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D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008934:Mitogens / Q000276:immunology; D019800:Phenol; D010636:Phenols / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D001679:Biogenic Amines; D008934:Mitogens; D010636:Phenols; D019800:Phenol