31 research outputs found

    Metabolism of phenol and hydroquinone to reactive products by macrophage peroxidase or purified prostaglandin H synthase.

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    Macrophages, an important cell-type of the bone marrow stroma, are possible targets of benzene toxicity because they contain relatively large amounts of prostaglandin H synthase (PHS), which is capable of metabolizing phenolic compounds to reactive species. PHS also catalyzes the production of prostaglandins, negative regulators of myelopoiesis. Studies indicate that the phenolic metabolites of benzene are oxidized in bone marrow to reactive products via peroxidases. With respect to macrophages, PHS peroxidase is implicated, as in vivo benzene-induced myelotoxicity is prevented by low doses of nonsteroidal anti-inflammatory agents, drugs that inhibit PHS. Incubations of either 14C-phenol or 14C-hydroquinone with a lysate of macrophages collected from mouse peritoneum (greater than 95% macrophages), resulted in an irreversible binding to protein that was dependent upon H2O2, incubation time, and concentration of radiolabel. Production of protein-bound metabolites from phenol or hydroquinone was inhibited by the peroxidase inhibitor aminotriazole. Protein binding from 14C-phenol also was inhibited by 8 microM hydroquinone, whereas binding from 14C-hydroquinone was stimulated by 5 mM phenol. The nucleophile cysteine inhibited protein binding of both phenol and hydroquinone and increased the formation of radiolabeled water-soluble metabolites. Similar to the macrophage lysate, purified PHS also catalyzed the conversion of phenol to metabolites that bound to protein and DNA; this activation was both H2O2- and arachidonic acid-dependent. These results indicate a role for macrophage peroxidase, possibly PHS peroxidase, in the conversion of phenol and hydroquinone to reactive metabolites and suggest that the macrophage should be considered when assessing the hematopoietic toxicity of benzene

    Evaluations of 1990 PRISM design revisions

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    Analyses of the 1990 version of the PRISM Advanced Liquid Metal Reactor (ALMR) design are presented and discussed. Most of the calculations were performed using BNL computer codes, particularly SSC and MINET. In many cases, independent BNL calculations were compared against analyses presented by General Electric when they submitted the PRISM design revisions for evaluation by the Nuclear Regulatory Commission (NRC). The current PRISM design utilizes the metallic fuel developed by Argonne National Laboratory (ANL) which facilitates the passive/``inherent`` shutdown mechanism that acts to shut down reactor power production whenever the system overheats. There are a few vulnerabilities in the passive shutdown, with the most worrisome being the positive feedback from sodium density decreases or sodium voiding. Various postulated unscrammed events were examined by GE and/or BNL, and much of the analysis discussed in this report is focused on this category of events. For the most part, the BNL evaluations confirm the information submitted by General Electric. The principal areas of concern are related to the performance of the ternary metal fuel, and may be resolved as ANL continues with its fuel development and testing program
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