Benzo(a)pyrene-induced anemia and splenomegaly in NZB/WF1 mice.
Benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon, is a known immunomodulator. At high doses, BaP is immunosuppressive but at low doses it can enhance the immune response. Studies were conducted to determine if BaP would exacerbate the development of autoimmune disease in genetically prone NZB/WF1 mice. Five week old female NZBW/F1 mice were exposed dermally to 5, 20 and 40 mg/kg BaP for 30 days. Vehicle mice were exposed to an acetone:olive oil mixture for 30 days. BaP did not increase total IgG, anti-DNP-HSA or anti-dsDNA antibody levels. However, hematological evaluation revealed a decrease in erythrocyte number, hemoglobin and hematocrit and an increase in mean corpuscular volume and red cell distribution width in the 20 and 40 mg/kg dose groups. Liver and spleen weights were increased in the high dose groups; however, an increase in spleen cell number was not observed. Histopathological evaluation revealed splenic red pulp expansion in a mouse treated with 40 mg/kg BaP. An increase in splenic CFU-e production was observed in mice treated with 20 and 40 mg/kg BaP. A decrease in splenic total B cells, total T cells, CD4(+) and CD8(+) T cells was observed in mice treated with 20 and 40 mg/kg BaP. An increase in splenic null cells (non-T, non-B cells) was also observed in the high dose groups, consistent with extramedullary hematopoiesis. Coombs' tests, flow cytometry and an immune-mediated hemolysis assay indicated that the anemia was not autoimmune-mediated. Although no change was observed in the percentage of reticulocytes in these animals, further bone marrow analysis is needed to determine if the anemia is due to bone marrow suppression, possibly caused by BaP exposure, or chemical-induced hemolysis, perhaps contributed to by erythrocyte fragility inherited from a parent strain, NZB, which spontaneously develops autoimmune hemolytic anemia and subsequent splenomegaly.
Booker
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Virginia Commonwealth University Richmond, Virginia, USA. bookerc@cder.fda.gov
White
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D000740:Anemia / Q000139:chemically induced*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001772:Blood Cell Count; D002452:Cell Count; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008814:Mice, Inbred NZB; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000473:pathology; D013163:Splenomegaly / Q000139:chemically induced* / Q000473:pathology
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D001564:Benzo(a)pyrene