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M W Tabor

Publications and source records attributed to M W Tabor.

30 records · Page 2Linked to original sources
PubMed1985

Metabolic activation of 3-(2-chloroethoxy)-1,2-dichloropropene: a mutagen structurally related to diallate, triallate, and sulfallate.

3-(2-Chloroethoxy)-1,2-dichloropropene (CP), a Salmonella promutagen that was recently isolated from a sample of residue organics previously concentrated from drinking water, is structurally related to three other chlorinated promutagens, the S-chloroallyl thiocarbamate herbicides diallate, triallate, and sulfallate. These four chloroallyl ether compounds were found to be similar with respect to strain specificity, potency, and requirement for specific metabolic activation. The 9,000g supernatant (S9) fractions from polychlorinated biphenyl Aroclor 1254- or phenobarbital-induced rats metabolized the four chloroallyl ethers to mutagenic products, whereas S9 from 3-methylcholanthrene-induced or uninduced rats did not. The metabolic activation of CP, diallate, and triallate to mutagens was catalyzed by the 100,000g microsomal pellet of S9 alone, but the activation of sulfallate to mutagenic metabolites required both microsomal and cytosolic fractions of S9. Direct-acting (minus S9) mutagenic metabolites of diallate and triallate could be extracted into methylene chloride from S9 incubation mixtures. Incubations containing S9 and either sulfallate or CP did not yield methylene chloride-extractable metabolites with direct-acting mutagenic activity. On the basis of these results and those from previous studies on the metabolism of diallate, triallate, and sulfallate, a tentative model for the metabolic activation of CP is proposed in which this chloroallyl ether undergoes alpha-carbon hydroxylation to form multiple mutagenic products.

Allyl Compounds↗
PubMed1985

Analytical isolation, separation and identification of mutagens from nonvolatile organics of drinking water.

A general procedure has been developed for the concentration/fractionation of mutagenic residue organics from small, less than 50L, and large, to 1200L, volumes of drinking water obtained from a variety of sources. This procedure features concentration of the residue organics chromatographically by passage of the water through XAD-2 and XAD-7 resins in specially designed columns, details of which are given. The residue organics are eluted from the resins via organic solvents, followed by solvent removal and subsequent bioassay for mutagenicity. Then the residue organics are fractionated via a coupled bioassay/analytical fractionation method which progressively focuses to the bioactive constituents of the complex mixture of residue organics. In this report, results for the optimal operation and validation of the concentration system are given, using drinking water derived from an industrially polluted river system, a wilderness river system and a major aquifer system. The predominant type of mutagenesis observed for the residue organics isolated from these samples was direct-acting to the Salmonella tester strain, TA98, which was decreased by the addition of the metabolic activation system from the livers of rats previously treated with Arochlor 1254. Some TA100 direct-acting mutagenesis was observed for all samples. Fractionation of the residue organics indicated the mutagens to be nonpolar. Samples of residue organics collected over a period of a year from each type of drinking water showed no discernable pattern of mutagenesis versus season. The methodologies described in this paper provide a comprehensive approach for the concentration/isolation of residue organics from drinking water for studies to identify biohazardous compounds and to characterize these compounds biologically.

Animals↗
PubMed1983

Effects of metyrapone on microsomal-dependent Salmonella mutagenesis. Studies with chloroallyl ethers and model compounds.

Metyrapone (2-methyl-1,2-di-3-pyridyl-1-propanone, MTP) is used as an inhibitor of cytochrome P-450 enzymes, particularly those induced by phenobarbital (PB). We examined the effects of MTP on the microsomal dependent mutagenesis of a newly isolated promutagen, 3-(2-chloroethoxy)-1,2-dichloropropene (CP), three S-chloroallyl thiocarbamate herbicides, and four model promutagens aflatoxin B1 (AFB), 2-acetylaminofluorene (2AAF), 2-aminoanthracene (2AA) and benzo[a]pyrene (BP). Salmonella tester strains TA98, TA100 and TA1535 and liver microsomal preparations (S9) from rats induced with PB or Aroclor 1254 (PCB) were employed. For statistical analysis, mutagenesis data were transformed and subjected to two-way analysis of variance. Metyrapone alone was not mutagenic in the absence or presence of S9. In a dose-dependent manner, MTP inhibited mutagenesis of AFB for strains TA98 and TA100 and enhanced mutagenesis of 2AAF, 2AA and BP for these strains. 3-(2-Chloroethoxy)-1, 2-dichloropropene and the herbicides diallate, triallate and sulfallate are all chloroallyl ethers. They are similar in their mutagenesis for Salmonella with respect to strain specificity, mutagenic potency, and requirement for activation by specifically-induced microsomes. Metyrapone inhibited the mutagenesis of CP, triallate and sulfallate for strain TA100 in the presence of either PB- or PCB-induced S9, and had no apparent effect on diallate mutagenesis; the same results were obtained for TA1535 with PCB-induced S9. On this basis, the mutagenic activation of diallate appears to be different from that of the other chloroallyl ethers tested. Our results indicate that MTP can inhibit as well as enhance microsomal dependent mutagenesis for Salmonella. We conclude that MTP may be a useful tool in characterizing pathways for promutagen activation.

Allyl Compounds↗
PubMed1979

Changes in amniotic fluid glucose, beta-hydroxy-butyrate, glycerol, and lactate concentration in diabetic pregnancy.

Amniotic fluid glucose, beta OH butyrate, glycerol, and lactate concentrations were measured in 75 samples collected in the third trimester of pregnancy from 50 diabetic patients, all but four of whom required insulin. Increases in maternal fasting plasma sugar were accompanied by corresponding increases in amniotic fluid glucose and on occasion increases in amniotic fluid beta OH butyrate. These data correspond to previous reports of placental glucose transfer and in addition, provide statistically significant evidence of placental betaOH butyrate transfer since the hyperglycemic, hyperinsulinemic fetus of a diabetic mother would be a poor primary source for ketogenesis. Relatively poor correlation of elevated fluid levels of these solutes to fetal outcome probably reflects a low incidence of maternal hyperglycemia, ketogenesis. Relatively poor correlation of elevated fluid levels of these solutes to fetal outcome probably reflects a low incidence of maternal hyperglycemia, ketoacidosis, and over-all reduced neonatal morbidity-mortality rates in this group of metabolically well-controlled, predominantly insulin-requiring diabetic patients managed in a regional high-risk perinatal center.

Adult↗
PubMed1978

Sequence analysis of 5'[32P] labeled mRNA and tRNA using polyacrylamide gel electrophoresis.

Sequence analysis of 5'-[32P] labeled tRNA and eukaryotic mRNA using an adaptation of a method recently described by Donis-Keller, Maxam and Gilbert for mapping guanines, adenines and pyrimidines from the 5'-end of an RNA is described. In addition, a technique utilizing two-dimensional polyacrylamide gel electrophoresis for identification of pyrimidines within a sequence is described. 5'-[32P] Labeled rabbit beta-globin mRNA and N. crassa mitochondrial initiator tRNA were partially digested with T1- RNase for cleavage at G residues, with U2-RNase for cleavage at A residues, with an extracellular RNase from B. cereus for cleavage at pyrimidine residues and with T2-RNase or with alkali for cleavage at all four residues. The 5'-[32P] labeled partial digestion products were separated according to their size, by electrophoresis in adjacent lanes of a polyacrylamide slab gel and the location of G's, A's and of pyrimidines extending 60-80 nucleotides from the 5'-end of the RNA determined. Two-dimensional polyacrylamide gel electrophoresis was used to separate the 5'-[32P] labeled fragments present in partial alkali digests of a 5'-[32P] labeled mRNA. The mobility shifts corresponding to the difference of a C residue were distinct from those corresponding to a U residue and this formed the basis of a method for distinguishing between the pyrimidines.

Animals↗
PubMed1976

Rapid determination of dipicolinic acid in the spores of Clostridium species by gas-liquid chromatography.

A gas-liquid chromatographic procedure has been developed to quantitate dipicolinic acid in bacterial spores. The culture, washed from a plate, was hydrolyzed with acid containing the internal standard, pyridine-2,4-dicarboxylate, and then extracted into methyl isobutyl ketone. The internal standard and dipicolinic acid were then extracted into a small volume of trimethylphenylammonium hydroxide. Injection of the resultant quaternary ammonium salts into a gas chromatograph yielded, via thermal decomposition, the methyl ester derivatives of the dipicolinic acid and the internal standard. The amount of dipicolinic acid in the sample was determined from a standard curve. The method was sensitive to 100 ng of dipicolinic acid per sample and was 1,000 to 5,000 times more sensitive than the commonly used methods. Preparation of the sample required less than 1.5 h and less than 15 min of the analyst's time.

Bacillus↗
PubMed1976

Progesterone and estrogen control of uterine prostaglandin dehydrogenase activity during deciduomal growth.

Prostaglandin, dehydrogenase activity was determined in deciduomal and myometrial tissues during growth and regression of the deciduoma during pseudopregnancy. The hormonal control of prostaglandin dehydrogenase activity in these tissues was determined in experiments with ovariectomized pseudopregnant rats. Prostaglandin dehydrogenase activity for both prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in deciduomal and myometrial tissues increased during the growth of the deciduoma and decreased during the regression phase. No prostaglandin dehydrogenase activity was detected in non-decidualized pseudopregnant rat uteri. In ovarictomized pseudopregnant rats, progesterone and estrogen increased prostaglandin dehydrogenase activity for PGE1 in the deciduoma and myometrium; no synergistic action of the hormones was observed. Progesterone increased prostaglandin dehydrogenase activity for PGF2alpha in the deciduoma, but had no effect in the myometrium. The increases during decidualization in dehydrogenase activity for PGE1 and PGF2alpha, and the enhanced inactivation of these luteolytic substances would provide an explantation for the prolonged pseudopregnancy which results from decidualization of the uterus.

Alcohol Oxidoreductases↗
PubMedDate not supplied

Enzyme induction by L-buthionine (S,R)-sulfoximine in cultured mouse hepatoma cells.

Induction of Phase II enzymes of the [Ah] gene battery by L-buthionine (S,R)-sulfoximine (BSO) and other agents was examined in mouse hepatoma Hepa-1c1c7 cells. BSO, a nonelectrophilic inhibitor of gamma-glutamylcysteine synthetase (GCS), is routinely used to examine the toxicological implications of GSH depletion. Exposure to BSO for 24 h produced a 75-85% depletion of GSH levels, proportional to the inhibition of GCS activity, as well as small increases in the UDP-glucuronosyltransferase (UGT, 60%) and glutathione transferase (GST, 30%) enzyme activities in Hepa-1 wild-type (wt) cells. However, for the NAD(P)H:menadione oxidoreductase (NMO1) and cytosolic aldehyde dehydrogenase class 3 (AHD4) enzyme activities, BSO produced larger increases (110% and 170%, respectively). The mechanisms of NMO1 and AHD4 induction were examined further. In Hepa-1 wt cells, NMO1 and AHD4 activities were increased by the aromatic hydrocarbon inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and by the electrophile tert-butylhydroquinone (tBHQ), known inducing agents for these enzymes. However, NMO1 and AHD4 were induced in Ah receptor nuclear translocation-defective mutant (c4) cells by BSO and tBHQ, but not by TCDD, suggesting that the induction by BSO and tBHQ is not Ah receptor-mediated. In wt cells, N-acetylcysteine produced a concentration-dependent increase in intracellular cysteine levels, but not GSH levels, in the absence or presence of BSO. Furthermore, N-acetylcysteine had no effect on NMO1 activity under any conditions examined, suggesting that GSH levels per se, rather than change in overall thiol status, might be mediating increased NMO1 activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoacyltransferases↗
PubMedDate not supplied

Exogenous iron overload in perinatal hemochromatosis: a case report.

We report an infant with fatal neonatal liver disease in whom efforts to correct an associated unremitting anemia resulted in massive exogenous iron overload that was expressed as perinatal hemochromatosis (PH). Levels of iron and copper were elevated in multiple tissues. Echovirus subtype 9, recovered from the urine at age 3 weeks, may have been etiologic in the liver failure. PH is best viewed as a definable phenotype with an undefined genetic and/or environmental basis that emerges only in the context of severe perinatal liver disease. The absence of hemosiderin in splenic and bone marrow reticuloendothelial (RE) cells of our patient suggests an important role for RE cell dysfunction.

Anemia↗