dinitrobenzenes and Anemia

Dinitrotoluene (DNT) is a nitroaromatic explosive used in propellant mixtures and in the production of plastics. Isomers of DNT were administered daily via oral gavage to male Sprague-Dawley rats for 14 days to determine the subacute toxicity of individual isomers of DNT. The 3,5-DNT isomer was the most toxic isomer, inducing weight loss and mortality within 3 days. Cyanosis and anemia were observed for all isomers. Exposure to 2,4-, 2,6-, and 3,5-DNT resulted in decreased testes mass and degenerative histopathological changes. Increased splenic mass was observed for 2,4-, 2,6-, and 2,5-DNT. Extramedullary hematopoiesis of the spleen was noted for all isomers, while lymphoid hyperplasia of the spleen was noted for all isomers except 2,5-DNT. Increased liver mass was observed for 2,3-DNT and 3,4-DNT. Hepatocellular lesions were observed for 2,6-DNT and 2,4-DNT. Neurotoxic effects were noted for 3,4-DNT, 2,4-DNT, and 3,5-DNT.

Topics: Anemia; Animals; Cerebellum; Cyanosis; Dinitrobenzenes; Isomerism; Liver; Male; Neurotoxicity Syndromes; Rats; Rats, Sprague-Dawley; Spleen; Structure-Activity Relationship; Testis; Toxicity Tests, Subacute

Mice lacking the homeodomain transcription factor Nkx2-3 are either asplenic or develop a spleen of significantly reduced size with poorly organized white pulp. In this report, we analyze the effect of this mutation on B lymphocyte development and differentiation. Follicular dendritic cells in spleen, but not lymph node, of Nkx2-3(-/-) mice fail to express a developmental Ag (follicular dendritic cell-M2) and show an abnormal association with B cells, despite essentially normal expression of several chemokine genes. Bone marrow reconstitution studies show the splenic disorganization and absence of marginal zone B cells to be of stromal rather than hemopoietic origin. Furthermore, Nkx2-3(-/-) mice show an excess of conventional B cells in mesenteric lymph node and peritoneal cavity, whereas transitional B cells are rare in spleen but overrepresented in bone marrow. Finally, immunization of Nkx2-3(-/-) mice with a T cell-dependent Ag elicits clusters of germinal center B cells, although these fail to develop to the same extent as in controls and there is no evidence of affinity maturation in serum Ab. Similarly, Ab-forming cells fail to aggregate into foci early in the response. Collectively, these data indicate a substantial role for Nkx2-3 in the correct association of lymphocytes and splenic stromal elements that is independent of chemokine expression.

Topics: Anemia; Animals; Antibody Formation; Antigens, T-Independent; B-Lymphocyte Subsets; Bone Marrow Transplantation; Cell Differentiation; Chemokines; Dendritic Cells, Follicular; Dextrans; Dinitrobenzenes; Female; Gene Expression Regulation; Haptens; Hemocyanins; Homeodomain Proteins; Immunoglobulins; Leukocytosis; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Spleen; Stromal Cells; T-Lymphocyte Subsets; Zebrafish Proteins

No significant differences of Km or Vmax could be demonstrated for the initial rate (0-3 min) of iron uptake by preparations of isolated duodenal mucosal epithelial cells from normal or sex-linked anemic (sla) mice. Isolated cells from sla mice do, however, take up significantly more iron than normal cells after 20-min incubation. Upon reincubation with various types of mobilizing agents, the amount of iron released from, and the amount of iron remaining in, cells from sla mice was significantly elevated compared to control values. The percentage of iron released was the same for both types of cells, for all mobilization media employed. The current data, in conjunction with previous studies that showed deficient mucosal to serosal transport of iron in everted duodenal sacs from sla mice, suggest that the lesion in these mice may be located between the mucosal cell and the vascular compartment rather than in the mucosal cell.

Topics: Anemia; Animals; Buffers; Cell Survival; Dinitrobenzenes; Duodenum; Hydrogen-Ion Concentration; Intestinal Mucosa; Iron; Kinetics; Mice; Mice, Inbred C57BL; Rotenone

Topics: Acute Disease; Adult; Anemia; Dinitrobenzenes; Humans; Middle Aged; Nitrobenzenes; Occupational Diseases