Search PubMed⌕ Search

Biomedical subjects

E D Wagner

Publications and source records attributed to E D Wagner.

At least 37 records · Page 2Linked to original sources
PubMed1994

Comparative mutagenicity of plant-activated aromatic amines using Salmonella strains with different acetyltransferase activities.

Plant systems can activate aromatic amines into mutagens. In the plant cell/microbe coincubation assay, we earlier demonstrated that 2-aminofluorene and m-phenylenediamine were activated by plant cells into mutagens with reversion at the hisD3052 allele in Salmonella typhimurium strain TA98 as the genetic endpoint. New derivatives have been developed which possess elevated levels of acetyl-CoA:N-hydroxyarylamine O-acetyltransferase which are very sensitive to N-hydroxylated amines [Watanabe et al., 1990: Mutat Res 234:337-348]. The objectives of this research were to examine Salmonella strains with different acetyltransferase activities in the plant cell/microbe coincubation assay with a series of structurally related aromatic amines. The hypothesis tested was whether and to what degree a plant-activated metabolite of these aromatic amines could serve as a substrate for bacterial O-acetyltransferase and induce mutation in Salmonella. Every aromatic amine examined was activated by plant cells with YG1024 (the strain with elevated O-acetyltransferase activity) as the genetic indicator organism. The rank order of the mutagenic responses of YG1024 to the plant-activated aromatic amines was 2-aminofluorene > benzidine > m-phenylenediamine > 4-aminobiphenyl > 2,4-diaminotoluene > 2-naphthylamine. This rank order was expressed by TA98 but to a much lower degree. There was a very slight mutagenic response observed in TA98/1,8-DNP6 (a strain lacking O-acetyltransferase activity) with the plant-activated metabolites of benzidine and 4-aminobiphenyl. We conclude that the plant-activated aromatic amines are substrates for bacterial O-acetyltransferases.

2-Naphthylamine↗
PubMed1993

Characterization of stable high molecular weight mutagenic product(s) of plant-activated m-phenylenediamine.

Monocyclic aromatic amines are environmental contaminants and many are promutagens and procarcinogens. Cultured tobacco cells, strain TX1, activated m-phenylenediamine into a frameshift mutagen that reverted the hisD3052 allele in Salmonella typhimurium strains TA98 and YG1024. However, the plant-activated products were refractory in strain TA98/1,8-DNP6. This indicated that these plant-activated products were substrates for bacterial acetyl-CoA: N-hydroxyarylamine O-acetyltransferase. A stable, high molecular weight (> 300 kDa) proximal mutagen was isolated by molecular ultrafiltration membranes. No parent compound was associated with the isolated mutagenic fraction. The high molecular weight fraction induced mutation in S. typhimurium strains TA98, YG1021 and YG1024. From these data we propose a model for the plant-activation of aromatic amine promutagens.

Acetyltransferases↗
PubMed1991

Diethyldithiocarbamate suppresses the plant activation of aromatic amines into mutagens by inhibiting tobacco cell peroxidase.

Diethyldithiocarbamate is an antimutagen and repressed the activation of promutagens by plant systems. Earlier work implicated the involvement of tobacco cell (TX1) peroxidases in the plant cell activation of aromatic amines. We now present data that diethyldithiocarbamate represses the activation of 2-aminofluorene and m-phenylenediamine by inhibiting intracellular TX1 peroxidases under in vivo conditions. Concentrations of diethyldithiocarbamate that caused a 50% repression of TX1 cell activation of 2-aminofluorene and m-phenylenediamine also induced a 50% inhibition of TX1 cell peroxidase activity. Diethyldithiocarbamate in a concentration range between 25 and 500 microM directly inhibited peroxidase activity in TX1 cell homogenates in a concentration-dependent manner. Similar results were observed with purified horseradish peroxidase. The kinetics of peroxidase activity were studied in homogenates from control cells and cells treated with 750 microM and 25 mM diethyldithiocarbamate. There was no significant difference among the Km values among the three groups with a mean (+/- standard error) Km of 2.58 +/- 0.23 mM. However, the Vmax differed from 4.02 to 2.12 nmoles tetraguaiacol/min/micrograms protein, in the control and in the 25 mM diethyldithiocarbamate treatment group, respectively. These data indicate that diethyldithiocarbamate is a non-competitive inhibitor of TX1 cell peroxidase.

Biotransformation↗
PubMed1990

The biochemical mechanisms of the plant activation of promutagenic aromatic amines.

Using specific monooxygenase and oxidase inhibitors in a plant cell/microbe coincubation assay, the biochemical mechanisms of the plant activation of two aromatic amines were compared. The biological endpoints included mutation induction, inhibition of mutagenicity, viability of the plant cells (activating system), and viability of the microbial cells (genetic indicator organism). The activation of m-phenylenediamine by TX1 cells was mediated by enzyme systems that were inhibited by diethyldithiocarbamate, potassium cyanide, methimazole, (+)-catechin or acetaminophen. The inhibition by metyrapone was attended by toxicity in the plant cells. These data implicate a TX1 cell peroxidase and a FAD-dependent monooxygenase in the plant activation of m-phenylenediamine. The TX1 cell activation of 2-aminofluorene was inhibited by diethyldithiocarbamate, 7,8-benzoflavone, acetaminophen or (+)-catechin. An additional pathway of the plant cells in the activation of 2-aminofluorene may involve a cytochrome P-448-type N-hydroxylase.

Acetaminophen↗
PubMed1989

Effects of specific monooxygenase and oxidase inhibitors on the activation of 2-aminofluorene by plant cells.

Using specific inhibitors, a plant cell/microbe coincubation assay was employed to investigate biochemical mechanisms of plant activation. The biological endpoints of mutation induction, inhibition of mutagenicity and viability of the plant-activating system as well as viability of the microbiological indicator were simultaneously assayed from the same reaction tube. We investigated six inhibitors of monooxygenases and oxidases (diethyldithiocarbamate, methimazole, metyrapone, (+)-catechin, 7,8-benzoflavone and potassium cyanide). The activation of 2-aminofluorene by TX1 cells was mediated by an enzyme system(s) that was inhibited by microM amounts of diethyldithiocarbamate or 7,8-benzoflavone. (+)-Catechin (at low concentrations) or methimazole enhanced the activation of 2-aminofluorene while higher concentrations of (+)-catechin were inhibitory. These data indicate that a significant pathway of the plant activation of 2-aminofluorene is via a cytochrome P-448-type N-hydroxylase. The presence of a FAD-dependent monooxygenase was not detected.

Benzoflavones↗
PubMed1989

Transbronchial fine-needle aspiration. Reliability and limitations.

Transbronchial needle aspiration is a new method of sampling pulmonary, paratracheal, and mediastinal masses. A total of 116 aspirations of the lung performed during a two-and-a-half-year period were reviewed. The results were compared with those of bronchial wash, bronchial brush, sputum, transbronchial forceps biopsy, and histologic material subsequently obtained during surgery or at autopsy. Clinical information was also reviewed. Transbronchial needle aspiration was performed on 104 patients, yielding 116 specimens. With the use of a combination of aspiration, wash, brush, sputum, and forceps biopsy, malignancy was detected in 48 patients. Open biopsy, mediastinoscopy, and transcutaneous needle aspiration increased the number of malignant neoplasms detected to 72. The tumors were detected in 67% of these 72 cases by a combination of all bronchoscopic methods. Transbronchial aspiration correctly identified 36% of malignant cases compared with 35% identified by wash, 39% by brush, 25% by sputum, and 59% by forceps biopsy. The overall accuracy of the techniques was 56% for aspiration, 48% for wash, 56% for brush, 35% for sputum, and 71% for forceps biopsy. Malignant cases were associated with cellular transbronchial aspirates, good preservation of cell detail, and a high degree of cytologic/histologic correlation regarding cell type. Transbronchial fine-needle aspiration has the potential for improving the diagnostic ability of bronchoscopy. However, the high incidence of false negative diagnoses is the main limitation for the technique, and the responsible factors are discussed.

Adult↗
PubMed1988

The plant cell/microbe coincubation assay for the analysis of plant-activated promutagens.

The preincubation and suspension procedures of the plant cell/microbe coincubation assay are described and the activation of 2-aminofluorene and m-phenylenediamine by cultured tobacco, cotton, carrot and maize cells is compared. The assay measures the plant activation of promutagens into genotoxins detected in Salmonella typhimurium as well as toxicity in plant and microbial cells. At concentrations of 2-aminofluorene 0-0.5 mumoles/reaction tube, the rank order of the efficiency of activation by plant cells was tobacco much greater than cotton greater than carrot. Cultured maize cells did not activate 2-aminofluorene. The tobacco cell activation of 2-aminofluorene was inhibited 50% by 750 microM diethyldithiocarbamate under conditions that did not affect the cell viability. Tobacco cells were also the most efficient plant cells in activating m-phenylenediamine (0-5 mumoles/reaction tube). The 'biological affinity' of m-phenylenediamine for the activation system in tobacco cells was approximately 100 microM.

Biotransformation↗
PubMed1985

Induction of micronuclei in maize root-tip cells and a correlation with forward mutation at the yg2 locus.

A standard protocol for a micronucleus assay in root tips of Zea mays was developed and calibrated using 137Cs gamma radiation, ethylmethanesulfonate (EMS), and N-ethyl-N-nitrosourea (ENU). The root tips were sampled 1, 3, and 5 days after the treatment period. Primary root tips (sampled 1 day after treatment) were the most responsive with the highest frequencies of micronuclei. The frequencies then decreased to control values after 3 days. By treating the same kernels for this assay and the yellow-green-2 (yg2) forward mutation assay, it was possible to analyze and compare the induction kinetics of micronuclei formation in root-tip cells and forward mutation at the yg2 locus in leaf primordial cells. Forward mutation at the yg2 locus by gamma rays, EMS, or ENU exhibited one hit kinetics. The induction of micronuclei demonstrated nonlinear kinetics with a significant increase over controls above 200 rads gamma rays, 10 mM EMS, or 250 microM ENU. ENU induced a higher frequency of micronuclei at all treatment concentrations than did gamma radiation or EMS. The data suggest that a higher relative proportion of yg2 mutant sectors induced by ENU may be due to chromosome aberrations than those induced by gamma radiation or EMS.

Cell Nucleus↗
PubMed1984

Calibration of the maize yg2 assay using gamma radiation and ethylmethanesulfonate.

A standard protocol for the yellow-green-2 (yg2) forward mutation assay in Zea mays is proposed. A detailed calibration of the assay using 137Cs gamma rays and ethylmethanesulfonate (EMS) was conducted. Gamma ray-induced mutant sectors in leaves 4 and 5 exhibited one-hit kinetics. The radiation doses ranged from 25 to 500 rads. The mean induced mutation rate per rad of gamma radiation was 4.54 X 10(-6). This value was constant for the primordial cells of leaves 4 or 5. The induction of forward mutation by EMS also exhibited one-hit kinetics in the concentration range 0.25-20 mM (0.33-23.54 mumol EMS/kernel). The mean induced mutation rate per mM EMS was 1.79 X 10(-4), and the mean induced mutation rate per mumol of EMS per kernel was 1.52 X 10(-4). Using the induced mutation rates for gamma radiation and EMS, the rad equivalent was calculated. One rad of gamma radiation is equivalent to the exposure of a 2.53 X 10(-5) M EMS solution or to 2.99 X 10(-8) mol of EMS per kernel.

Ethyl Methanesulfonate↗
PubMed1984

An evaluation of the genotoxic properties of herbicides following plant and animal activation.

Commercial and technical grades of 11 herbicides and 13 combinations of commercial grade herbicides were evaluated for their genotoxic properties with Salmonella typhimurium, Saccharomyces cerevisiae directly and following plant and animal activation, or with Zea mays. The herbicides were related by their use in commercial corn (maize) production. Commercial grade formulations of each herbicide and combination of herbicides were also evaluated in situ with the pollen waxy locus assay of Z. mays. Eradicane and bifenox were negative in all assays. Alachlor, propachlor, procyazine and SD50093 (a formulation of cyanazine plus atrazine) were positive in one assay. Cyanazine, dicamba and metolachlor were positive in 2 assays. Atrazine, simazine and butylate were tested only in situ. Atrazine and simazine were positive and butylate was negative. Of the combinations of herbicides evaluated with the 3 genetic assays, alachlor plus bifenox and procyazine plus metolachlor were positive in 1 assay and metolachlor plus atrazine was positive in 2 assays. Of the combinations of herbicides evaluated only in situ, butylate plus atrazine, eradicane plus atrazine, eradicane plus cyanazine and metolachlor plus cyanazine were positive while butylate plus cyanazine was negative.

Animals↗
PubMed1983

Pinworm prevalence in California elementary school children, and diagnostic methods.

The pinworm prevalence among 302 children tested in 1980 in five Southern California elementary schools was determined to be 11.6%. The range was 7.3-15.4%. In a 1982 study involving 158 children in six schools, the prevalence was 21.6% (range 11.1-38.9%). The results of these studies are compared with those of a similar prevalence study done in the same area and in some of the same schools during the 5-year period 1960-1964. The prevalence for the earlier period, involving 700 children in six schools, was 34.6%, and ranged from 29.2-43.0%. A new, flexible, plastic pinworm slide was used in the 1980 and the 1982 studies. In the 1982 study, this diagnostic method was evaluated and compared for efficiency and use against the standard cellulose tape/glass slide. The two are equally effective in picking up eggs, and in reading quality. The plastic slide is easier to use and does not break.

California↗
PubMed1982

An evaluation of the genotoxic properties of insecticides following plant and animal activation.

Commercial and technical grades of 10 insecticides were evaluated for genotoxicity with Salmonella typhimurium and Saccharomyces cerevisiae directly and following plant and animal activation. Field-grade formulations of each insecticide were also tested for mutations at the waxy (wx) locus in Zea mays in situ. Carbofuran, chloropyrifos, curacron, metham and phorate were negative in all assays. Ethoprop and terbufos were each positive in 1 assay, and chlordane, fonofos and heptachlor were each positive in 2 assays. Fonofos and terbufos were positive directly and following animal activation while chlordane and heptachlor were positive following both plant and animal activation. Chlordane, ethoprop, and heptachlor were positive in Z. mays.

Animals↗
PubMed1981

Germinal cell mutagenesis in specially designed maize genotypes.

We have used three inbreds of Zea mays in our in situ and laboratory studies in environmental mutagenesis. Inbred W22 plants homozygous for wx-C were used in a study to detect the possible mutagenic properties of 32 pesticides or combination of pesticides under modern agricultural conditions. The large numbers of pollen grains analyzed and the ease in detecting mutant pollen grains enabled us to treat the experimental plants with field recommended rates of pesticides. In a current study we are evaluating the possible mutagenicity of Chicago municipal sewage sludge. We are measuring the frequency of mutant pollen grains in inbred M14 at both the wx-C and wx-90 heteroalleles. These plants were exposed to various concentrations of municipal sewage sludge under field conditions. We have inbred Early-Early Synthetic for five generations and tested this inbred with known mutagens. Early-Early Synthetic is a rapidly maturing inbred growing from kernel to anthesis in approximately 4 weeks and attaining a height of approximately 50 cm. Plants of this inbred have been chronically treated with ethylmethanesulfonate (EMS) or maleic hydrazide (MH) under laboratory conditions and forward mutation at the wx locus was measured in the pollen grains. EMS and MH were mutagenic at concentrations of 1 microM and 10 nM, respectively. The concentrations of EMS and MH were calibrated in Early-Early Synthetic to a linear increase in the frequency of forward mutant pollen grains. The construction of a maize monitor for environmental mutagens is currently in progress. This assay will measure forward or reverse mutation at the wx locus in pollen grains, point mutation in somatic cells and will incorporate a cytogenetic endpoint in root-tip cells.

Ethyl Methanesulfonate↗
PubMed1978

In vivo effects of mebendazole and levamisole in the treatment of trichuriasis and ascariasis.

The anthelmintic drugs mebendazole (Vermox) and levamisole were tested in patients for their possible ovicidal effects on the eggs of Trichuris trichiura and Ascaris lumbricoides. The patients studied were 20 Africans of Sierra Leone, and 11 children of Nassau, Bahamas. Egg counts were made before treatment, and for 5 consecutive days following treatment. Eggs were incubated in 2.5% aqueous potassium dichromate and percentages of larval development were determined. Mebendazole completely inhibited the development of the eggs of T. trichiura by day 3 of the follow-up period. The ovicidal action of mebendazole on the eggs of A. lumbricoides was determined to be 64.8% by day 5 of the follow-up study. Levamisole had little (11.6%) ovicidal action on the eggs of T. trichiura and no ovicidal activity for A. lumbricoides.

Adult↗