Leukemia and bone marrow microenvironment.
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Biomedical subjects
Publications and source records attributed to B Nath.
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Micronucleus induction and phagocytosis in V79 and CHO cells treated with diesel emission particles (DEP) were studied. After separation of the sample into supernatant and sediment fractions, the genotoxic activity of DEP was shown to reside in the supernatant fraction for the DMSO-extracted sample, and in the sedimented fraction for the dipalmitoyl lecithin (DPL), a primary component of pulmonary surfactant, dispersed sample. More particles from DMSO sediment samples were phagocytized than DPL sediment by both types of cells. This had no effect, however, on micronucleus induction. CHO cells phagocytized fewer particles, but gave a higher number of micronuclei than V79 cells. CHO cells seem to be more sensitive to DEP. Evidently, micronucleus induction is not the result of phagocytosis per se, but is due to the different response of the indicator cells to the DEP sample tested. These results further indicate that most, if not all, genotoxic compounds associated with DEP can be extracted by DMSO and that genotoxic activity associated with DEP inhaled into the lung may also be expressed by dispersion of particles in pulmonary surfactant.
A RIA for the antithyroid drug methimazole [1-methyl-2-mercaptoimidazole (MMI)] has been developed. A MMI derivative, 5-COOH-MMI, was conjugated to porcine thyroglobulin, and antibodies to the conjugate were raised in rabbits. [35S]MMI was used as the tracer. At a final antibody dilution of 1:100, the assay could detect MMI in amounts as low as 2.5 ng. The putative MMI metabolites 3-methyl-2-thiohydantoin and 1-methylimidazole had minor cross-reactivities of 2.1% and 0.5%, respectively. There was no effect of serum proteins on MMI immunoactivity. MMI was given orally to normal subjects (n = 6), hyperthyroid patients (n = 5), patients with hepatic cirrhosis (n = 4), and normal lactating women (n = 4). After a single dose of 60 mg, peak MMI levels were similar in the normal subjects and the hyperthyroid patients (approximately 1.5 micrograms/ml). Patients with hepatic cirrhosis had similar peak MMI serum levels [1.31 +/- 0.3 (+/- SEM) micrograms/ml], but the half-time of MMI disappearance from serum was significantly prolonged compared with the normal value (21.2 vs. 6.0 h; P less than 0.001). The lactating women received 40 mg MMI as a single dose. Over the next 8 h, mean MMI levels in serum and milk were nearly identical, with a mean serum to milk ratio of 1.03 +/- 0.16. A total of 70.0 +/- 6.0 micrograms MMI was excreted in the milk over the 8-h time period. This amount of MMI could affect neonatal thyroid function.
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