Inhibition of humoral immunity and mitogen responsiveness of lymphoid cells following oral administration of the heterocyclic food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to B6C3F1 mice.
In these studies, the food promutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was evaluated for its immunotoxicity in B6C3F1 mice following oral 5-day dosing at total doses of 50 and 150 mg/kg. Results indicated that PhIP produced a dose-dependent suppression of the humoral immune response of spleen cells to sheep erythrocytes, with a 50% decrease in the number of PFC detected at the 150 mg/kg dose of PhIP. A 40-90% inhibition of the phytohemagglutinin (PHA) response of spleen cells, mesenteric lymph nodes (MLNs), and Peyer's patch (PP) lymphocytes was seen in the treatment groups. The lipopolysaccharide (LPS) response was somewhat more variable and less affected with 20-30% inhibition observed in the spleen and PPs, whereas PhIP increased the LPS response in the MLNs. There was no effect of PhIP on cell recovery or viability in any of the treatment groups. Flow cytometry analysis revealed a depletion of T cells (Thy 1.2+ cells) and a slight increase in B cells (Ly5+ cells) in the PPs. The percentage of B and T cells present in the spleen and MLNs was unaffected by PhIP. These results demonstrate that the oral administration of PhIP produces immunotoxicity to mice, especially to lymphoid tissues present in the GI tract (i.e., PPs), and demonstrates that T cell mitogen (PHA) responses in PPs are the most sensitive indicator of PhIP-induced immunotoxicity.
Davis
D A
DA
University of New Mexico College of Pharmacy, Toxicology Program, Albuquerque 87131.
Archuleta
M M
MM
Born
J L
JL
Knize
M G
MG
Felton
J S
JS
Burchiel
S W
SW
D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007093:Imidazoles / Q000633:toxicity*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D008934:Mitogens / Q000037:antagonists & inhibitors; D009153:Mutagens / Q000633:toxicity*; D010581:Peyer's Patches / Q000276:immunology; D012756:Sheep / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
D000954:Antigens, Surface; D007093:Imidazoles; D008934:Mitogens; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine