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 B6C3F(1) MICE

In these studies, the food promutagen 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) was evaluated for its immunotoxicity in B6C3F(1 ) 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, wit h a 50% decrease in the number of PFC detected at the 150 mg/kg dose o f PhIP. A 40-90% inhibition of the phytohemagglutinin (PHA) response o f 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 recover y or viability in any of the treatment groups. Flow cytometry analysis revealed a depletion of T cells (Thy1.2(+) cells) and a slight increa se in B cells (Ly5(+) cells) in the PPs. The percentage of B and T cel ls present in the spleen and MLNs was unaffected by PhIP. These result s demonstrate that the oral administration of PhIP produces immunotoxi city to mice, especially to lymphoid tissues present in the GI tract ( i.e., PPs), and demonstrates that T cell mitogen (PHA) responses in PP s are the most sensitive indicator of PhIP-induced immunotoxicity. (C) 1994 Society of Toxicology.