Biomedical subjects

T Zenser

Publications and source records attributed to T Zenser.

3 recordsLinked to original sources

PubMed1996

Determination of benzidine, N-acetylbenzidine, and N,N'-diacetylbenzidine in human urine by capillary gas chromatography/negative ion chemical ionization mass spectrometry.

We report an isotope dilution mass spectrometry method using capillary gas chromatography/negative ion chemical ionization to quantitate urine concentrations of benzidine (BZ) and of its acetylated metabolites N-acetylbenzidine (ABZ) and N,N'-diacetylbenzidine (DABZ). Urine samples were purified by solid-phase extraction columns, reduced with LiAlH4/THF, and derivatized with pentafluoropropionic anhydride. The derivatives were measured by selected ion monitoring relative to deuterium-labeled internal standards. A detection limit as low as 0.5, 0.8, and 1.5 ppt for BZ, ABZ, and DABZ, respectively, can easily be achieved. Urinary concentrations of ABZ substantially exceed those of either BZ or of DABZ in workers exposed to BZ or BZ-based dyes. This method has been successfully used to measure BZ, ABZ, and DABZ in 1.0-ml urine samples collected from workers involved in manufacturing BZ and BZ-based dyes. The method should be applicable to the measurement of other aromatic amines and their acetylated metabolites.

Benzidines↗

PubMed1986

Metabolism and excretion of nitrofurothiazole bladder carcinogens.

Nitrofurothiazoles such as 2-amino-4-(5-nitro-2-furyl) thiazole (ANFT) and N-formylated ANFT (FANFT) are model compounds used in the study of chemical carcinogenesis. FANFT is a more potent uroepithelial carcinogen than ANFT but previous studies have shown extensive deformylation of FANFT to ANFT in vivo and ANFT to be the putative proximate carcinogen. To investigate this paradox, disposition of radiolabeled FANFT and ANFT was determined in rats prepared for clearance experiments. After 2 hr, 27.3 +/- 2.1% of recovered ANFT was excreted in urine compared to 44.2 +/- 1.8% of FANFT (P less than .001). In addition, approximately 20% of both FANFT and ANFT were excreted in bile after 2 hr. The disposition of nonradiolabeled FANFT and ANFT was also determined. The urinary excretion rate for ANFT with i.v. ANFT administration was 0.9 +/- 0.1 nmol/min. Following i.v. FANFT administration, the urinary excretion rate for ANFT was 49.7 +/- 8.6 nmol/min (P less than .001). The elimination half-lives were 23 +/- 3 and less than 5 min, for ANFT and FANFT, respectively. The differences in renal handling of ANFT and FANFT could not be accounted for by differences in protein binding. Large differences were found in urinary metabolite excretion between FANFT and ANFT administration. These results demonstrate deformylation dependent excretion (renal metabolic/excretory coupling) exists for FANFT resulting in much higher concentrations of ANFT reaching the urinary tract than when ANFT only is administered. Biliary excretion accounts for significant early clearance of both ANFT and FANFT. Renal metabolic/excretory coupling may explain the difference in uroepithelial carcinogenicity between FANFT and ANFT.

Animals↗

PubMed1976

Activation of murine lymphocytes by cyclic guanosine 3',5'-monophosphate: specificity and role in mitogen activity.

Cyclic guanosine 3',5'-monophosphate (cyclic GMP) stimulates nucleic acid synthesis in lymphocytes, and has been implicated as the intracellular effector of the actions of mitogenic agents on these cells. In the present study, we examined the specificity of the mitogenic activity of cyclic GMP and of its 8-bromo (Br) derivatives, and the effects of the T cell mitogens, concanavalin A, phytohemagglutinin, and staphylococcal entertoxin B (SEB) on the cyclic GMP content and guanylate cyclase activity of mouse splenic lymphocytes. Cyclic GMP and guanosine modestly increased the incorporation of [3H] thymidine into DNA by cultured lymphocytes, but were far less effective than their 8-Br-guanosine and 8-Br-5'-GMP exceeded that of 8-Br-cyclic GMP, when tested in the presence and absence of serum in the culture media. Combined addition of maximal doses of these nucleotides did not give additive stimulatory effects, suggesting an action on a common subpopulation of cells, and possibly a common mechanism. By contrast, cyclic AMP, 8-Br-cyclic AMP, 8-Br-adenosine, cholera toxin and prostaglandin E1 suppressed both basal [3H]thymidine incorporation and stimulation of this parameter by T-cell mitogens and the guanine nucleotides. Rapid effects of concanavalin A, phytohemagglutinin, SEB, guanosine, 5'-GMP, 8-Br-guanosine, and 8-Br-5'-GMP on the cyclic GMP content of murine lymphocytes could not be demonstrated. Similarly, concanavalin A, phytohemagglutinin and SEB failed to alter guanylate cyclase activity when added directly to cellular homogenates or pre-incubated with intact cells. Conversely, carbamylcholine rapidly increased lymphocyte cyclic GMP but was not mitogenic. These results are consistent with the hypothesis that cyclic GMP and cyclic AMP are antagonistic in their influence on lymphocyte mitogenesis. However, they also demonstrate that related nucleotides are more potent mitogens than cyclic GMP itself and suggest that activation of murine lymphocytes by concanavalin A, phytohemagglutinin and SEB may not be mediated by rapid increases in cellular cyclic GMP content. Since high concentrations of exogenous cyclic GMP and related nucleotides must be used to influence DNA synthesis, the biologic significance of this effect remains uncertain.

Animals↗