Protracted exposure of C57BL/6 mice to 300 ppm benzene depresses B- and T-lymphocyte numbers and mitogen responses. Evidence for thymic and bone marrow proliferation in response to the exposures

Abstract

Groups of C57BL/6J, male mice were exposed to 300 ppm benzene via inhalation for 115 exposures (6 h/day, 5 days/week), a regimen known to cause thymic lymphoma in these animals. The effects of these exposures on lymphoid parameters were determined by measuring the numbers of B- and T-lymphocytes and mitogen-induced proliferation of B- and T-lymphocytes in bone marrow, spleen, and thymus after 6, 30, and 115 exposures. The numbers of B-lymphocytes in bone marrow and spleen and the numbers of T-lymphocytes in thymus and spleen were found to be markedly reduced after all 3 periods. Mitogen-induced proliferation of bone marrow and splenic B-lymphocytes exhibited a progressive depression throughout the exposure period reaching a point of no observable response after 115 exposures. Splenic T-cell mitogen-induced proliferation was also markedly depressed throughout the exposures, but there was no evidence of a progressive decline in this response during the exposures. Bone marrow cellularity increased 3-fold and the numbers of thymic T-cells increased 15-fold in benzene-exposed mice between the 6th and 30th exposure. No corresponding increase in splenic cells was observed in benze-exposed mice during this interval. The marked increases in the numbers of cells in bone marrow and thymus are interpreted as arising from compensatory proliferation of a subpopulation of cells in response to the exposures. The absence of increases in cell number in the spleen is interpreted as reflecting the lack of lymphoid restorative capacity in this organ. The marked increases of thymic and bone marrow cellularity are discussed relative to the known ability of this benzene exposure regimen to produce thymic lymphoma in these animals.