Inhibition of lymphocyte activation in splenic and gut-associated lymphoid tissues following oral exposure of mice to 7,12-dimethylbenz[ a]anthracene

Abstract

The hypothesis that 7,12-dimethyl-benz[ a]anthracene (DMBA) suppresses immune function in mice via an inhibition of lymphocyte activation was examined in these studies. Daily exposure of B6C3F1 mice to DMBA (cumulative doses of 1.4 to 140 mg/kg) via the oral route for 14 days was found to inhibit phytohemagglutinin (PHA) and lipopolysaccharide mitogen responses in lymphoid cells obtained from the spleen, Peyer's Patches, and mesenteric lymph nodes. The 14 mg/kg cumulative dose of DMBA produced no significant decrease in the number of recovered viable cells, yet mitogen responses were suppressed by approximately 50% in the spleen and mesenteric lymph nodes, and by greater than 70% in the Peyer's Patches. DMBA inhibited PHA-induced Ca +2 mobilization measured by flow cytometry in each of these three lymphoid tissues. There was no change in the percentage of T cells recovered from the spleen, mesenteric lymph nodes, or Peyer's Patches. Peyer's Patch lymphocytes obtained from the GI tract appeared to be slightly more sensitive to inhibition of mitogen responsiveness and perhaps Ca +2 mobilization, potentially due to the oral route of exposure to DMBA. These studies provide evidence that DMBA inhibits early events associated with lymphocyte activation in mice.