A model for the induction of aplastic anemia by subcutaneous administration of benzene in mice.

Long-term exposure to benzene vapors is associated with hematological diseases such as leukemia, lymphoma and aplastic anemia. CD(1) male mice were randomly assigned to six groups: 1B(10), 1B(15), 1B(20), 2B(10), 2B(15), and 2B(20.) 1B mice were administered 2 ml/kg (1940 mg/kg) subcutaneous injection (in the dorsal region) of benzene 5 days a week, and 2B mice were exposed 3 days a week (Monday, Wednesday and Friday) until a total of 10, 15 and 20 doses were completed. About 48 h after treatment completion, leukocyte, erythrocyte, and bone marrow cells were counted, and spleen histopathology was analyzed. 1B(15) and 1B(20) mice showed lethargy and irritability, 80% body and 42% spleen weight loss (P<0.001), while body and spleen weight loss were less severe in 2B mice (12 and 48%, respectively). After exposure to 20 benzene doses, 1B(20) and 2B(20) mice showed decreased hemoglobin concentrations, and erythrocyte, leukocyte and bone marrow cell counts (37, 34, 80 and 50%, respectively in group 1B(20); P<0.001; and 12, 48, 62 and 62%, respectively in group 2B(20)). Thrombocytopenia occurred only in group 2B. Both benzene-treatment schemes caused aplastic anemia, however, the disease was masked by spleen toxicity in group 1B. Scheme 2 allowed mice survival and caused less non-hematological effects. We establish here a reproducible and inexpensive experimental model to induce aplastic anemia in mice by subcutaneous injection of 2 ml/kg benzene, using two short-term treatment schemes.