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Induction of multispored asci in two-spored strains of Saccharomyces cerevisiae by amitrole.

Although growth of two yeast strains characterized by consistent production of two diploid spores per ascus was inhibited in complex presporulation media containing amitrole, a fraction of the cells produced were able to form asci with more than two spores after transfer to acetate sporulation medium. Cells grown in a defined presporulation medium containing amitrole did not acquire this ability. The increase in spore numbers per ascus is attributed either to the induction by amitrole in growth medium of cells with more than one nucleus or to the restoration of normal meioses in the multispored asci.

Amitrole↗

Alveolar damage due to inhalation of amitrole-containing herbicide.

Amitrole-containing herbicides are commonly used by home and cottage owners for spraying grass. They are manufactured and distributed in the United States, Canada and throughout the world by several pharmaceutical/chemical industries under many different trade names, such as Amitrole-T, Amizol, Azolan, Cytrol and Weedazol. They have not been previously associated with pulmonary toxicity in man or laboratory animals. We describe the first case in which inhalation of amitrole herbicide resulted in diffuse, asymmetric, severe alveolar damage, which was reversed after treatment with high-dose corticosteroids.

Aged↗

[Mutation in the glmS gene responsible for the cell wall synthesis increases resistance to the herbicide amitrole in the cyanobacterium Synechocystis sp. PCC6803].

A DNA fragment transforming the cells of the cyanobacterium Synechocystis sp. PCC 6803 to amitrole (3-amino-1,2,4-triazole) resistance was cloned from the Atr2 mutant resistant to this herbicide. The transforming activity of the cloned fragment was shown to be related to the missence-mutation "Val250-->Leu250" in the glmS gene encoding glucosamine-6-phosphate synthase, a key enzyme of cell wall synthesis. The amino acid substitution is localized in the central nonconservative part of the GlmS protein, far from two reaction centers positioned at the ends of a polypeptide. It is suggested that the mutant protein has lost sensitivity to amitrole. In the wild type strain, this herbicide causes conditional glucosamine auxotrophy (exogenous glucosamine restores ability of the cells to row in the presence of the lethal amitrole concentrations). Val250 is proposed to be allosteric binding site of AM in the GlmS protein of cyanobacterium.

Amino Acid Sequence↗

Inhibition of carotenoid synthesis as a mechanism of action of amitrole, dichlormate, and pyriclor.

Amitrole (3-amino-s-triazole), dichlormate (3,4-dichlorobenzyl methylcarbamate), and pyriclor (2,3,5-trichloro-4-pyridinol) inhibited normal carotenogenesis in etiolated wheat (Triticum aestivum L. var. Coker 65-20) seedlings. Carotenoid precursors accumulated in treated plants. In dichlormate-treated plants, zeta-carotene accumulated, whereas phytofluene, phytoene, and zeta-carotene accumulated in amitrole- and pyriclor-treated plants. None of the herbicides interfered with protochlorophyllide synthesis or its conversion to chlorophyllide when etiolated plants were illuminated. Chlorophyll accumulated in treated plants exposed to light at 60 foot candles, but was unstable and partially destroyed by illumination at 4000 foot candles. These data suggest that the phytotoxicity of amitrole, pyriclor, and dichlormate is due to inhibition of the synthesis of carotenoids and to the consequent photodestruction of chlorophyll and chloroplast disruption.

Journal Article↗

The effect of amitrole (3-amino-1H-1,2-4-triazole) on cytokinin activity and sexual reproduction in the yeast Schizosaccharomyces octosporus.

Cytokinin activity in extracts from actively growing cultures of Schizosaccharomyces octosporus was greatly reduced by exposure to amitrole (5 X 10--3M). Amitrole treatment, at the same concentration, stimulated cell enlargment and ascus production in this organism. These data suggest that a relationship may exist between low levels of endogenous cytokinins, cell expansion in preference to cell division, and ascus formation.

Amitrole↗

Mutagenicity and toxicity of amitrole. II. Human lymphocyte culture tests.

Effects of amitrole (3-amino-1,2,4-triazole) on human leucocytes in culture were investigated. Amitrole interfered with lymphoblast transformation and inhibited cell growth in concentrations of 0.2% w/v and higher. Selected metaphases were examined for the presence of chromosome and chromatid aberrations. No clastogenic effects were observed.

Amitrole↗

Determination of the herbicide amitrole in water with pre-column derivatization, liquid chromatography and tandem mass spectrometry.

Amitrole is a widely used polar herbicide, difficult to isolate from water. Due to its persistence, it can easily pollute ground and surface waters used in drinking water production. A fully automated on-line SPE-HPLC (solid-phase extraction-high-performance liquid chromatography) method with atmospheric pressure chemical ionisation-tandem mass spectrometry detection is described for the determination of amitrole. A pre-column derivatization with 9-fluorenylmethoxycarbonyl chloride directly in the native aqueous sample allows an enrichment step by SPE and HPLC separation. Due to the sensitivity of tandem mass spectrometric detection, a limit of detection and quantification as low as 0.025 microg/l was achieved in drinking water and ground and surface water. Based on the constant ratio of two selected product ions together with the retention time, the identification is very selective and quantitation is very reliable. The performance characteristics of the described method fully meet the requirements set by the EU Drinking Water Directive: recoveries of >95% in drinking water and >75% in surface water were achieved, as well as RSD values for repeatability of <9% in drinking water and <12% in surface water (determined at a spiking level of 0.1 microg/l). The method was successfully applied to real samples of ground and surface water with actual concentration up to 1.1 microg/l.

Amitrole↗

Sporulation in single-spore isolates from amitrole-induced multispored asci of Saccharomyces cerevisiae.

Amitrole treatment causes multispored ascus production by cells of a yeast strain whose asci normally contain two diploid spores. Single spores were isolated from asci containing two to eight spores and their ability to germinate was determined. Cells in colonies grown from single spores sporulated in the same manner as the parent strain indicating that amitrole had not induced meiotic division in the developing asci.

Amitrole↗

Lack of combination hepatocarcinogenicity of harman, norharman and amitrole when given with NaNO2 in the rat.

N-nitrosocompounds, which induce cancers in various organs, may be formed endogenously with intake of amino compounds such as secondary amines and sodium nitrite (NaNO(2)) in combination. The present study was performed to investigate whether three amino compounds, 1-methyl-9H-pyrido[3,4-b]indole (harman), 9H-pyrido[3,4-b]indole (norharman) and 2-amino-1,3,4-triazole (amitrole), might be converted in vivo to compounds capable of promoting hepatocarcinogenesis when given with NaNO(2). However, in an 8-week model, no modifying potential was evident in terms of numbers and areas of putative preneoplastic glutathione S-transferase placental form (GST-P)-positive foci in any of the groups receiving paired treatments. These results demonstrate that combinations of harman, norharman and amitrole with NaNO(2) lack promoting effects for liver carcinogenesis in our medium-term bioassay system.

Amitrole↗

Studies on the action of pesticides upon the endocrines using in vitro human thyroid cells culture and in vivo animal models. I. Herbicides--aminotriasole (amitrol) and atrazine.

The action of aminotriasole (amitrol) and atrazine in doses of 0.001--1 mg and 0.0001--.01 mg/1.5 ml medium, respectively, upon cell cultures of human thyroid was studied in order to find out their influence on cell multiplication, proteic synthesis, enzymatic activity of thyroid cells, and hormonal synthesis. The results varied according to the dose utilized and the type of thyroid cell studied. The acute experiment carried out on rats treated 15 days with 500 ppm amitol and 50 ppm atrazine revealed variations in the T3, T4 and LH synthesis. Amitrol showed a strong inhibitory action on T3 and T4 secretion, whereas atrazine stimulated it.

Amitrole↗

The influence of auxin, cacodylic Acid, and amitrole on the abscission of petiole explants.

The influence of indoleacetic acid, cacodylic acid (hydroxy-dimethylarsine oxide), and amitrole (3-amino-1,2,4-triazole) on the petiole explant abscission rate was studied in three species. Indoleacetic acid increased the abscission rate in both bean (Phaseolus vulgaris L. var. Red Kidney) and Coleus (Coleus blumei Benth) at 10(-3) and 10(-4)m but had no effect on abscission in privet (Ligustrum ovalifolium). Cacodylic acid was found to stimulate abscission in explants of beans and privet, but not in Coleus. Amitrole did not stimulate abscission under any circumstance tested. In no case was the abscission rate dependent on the time at which any of the chemicals was applied. These data do not support the two-phase response of explants to applied auxin.

Journal Article↗

Simultaneous separation and on-line concentration of amitrole and benzimidazole pesticides by capillary electrophoresis with a volatile migration buffer applicable to mass spectrometric detection.

This study used capillary electrophoresis (CE) to investigate the simultaneous separation and on-line concentration of five pesticides: amitrole (AMT), carbendazim (MBC), 2-aminobenzimidazole (ABI), thiabendazole (TBZ) and 1,2-diaminobenzene (DAB). A volatile migration buffer was used for the investigation because of the applicability to mass spectrometric (MS) detection. They were separated completely at pH 4.0 as a result of changing pH using formic acid-ammonium formate buffer. Values of the dissociation constant for MBC and DAB estimated from the changes in the mobility with pH showed good agreement with values in the literature. Dissociation constants for AMT and TBZ were estimated. Limits of detection (LODs) for the analytes were on the ppm level with UV detection under the optimized separation condition. On-line concentration by simple stacking mode was not effective except to 2-aminobenzimidazole because of the peak tailing. The addition of formic acid to sample matrix improved the peak shapes. That improvement may be attributed to transient isotachophoretic effect. The concentration factors obtained from the comparison of the LODs were in the range of 7.6-27-fold. This concentration method was applied preliminarily to CE with MS detection.

Amitrole↗

Indomethacin induces small intestinal damage and inhibits amitrole-associated thyroid carcinogenesis in rats initiated with N-bis(2-hydroxypropyl)nitrosamine.

Effects of intestinal damage on thyroid carcinogenesis due to amitrole (AT) were examined in F344 male rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). In experiment 1, rats were provided with diet containing 0.03% AT for 20 weeks after a single subcutaneous injection of DHPN (2800 mg/kg body weight), and concomitantly received 0.01% indomethacin (IM) in the diet to cause small intestinal damage or 1% dextran sodium sulfate (DSS) in the drinking water for induction of colitis following a schedule of intermittent 1-week administration and 1-week withdrawal for a total of 10 times. Groups without AT- and/or IM or DSS treatment were also included. Histopathological examination revealed significant reduction in the incidence and multiplicity of follicular cell adenomas and adenocarcinomas in the group concomitantly treated with IM, but no change in the DSS group, as compared with the AT alone group. In experiment 2, rats were similarly fed diet containing AT for 3 weeks with concomitant IM or DSS treatment after a DHPN initiation, and serum thyroid stimulating hormone levels were found to be significantly elevated only in the IM case. The increase in thyroid follicular cell proliferation due to AT was also clearly suppressed in the group concomitantly treated with IM. From these findings, IM-induced intestinal damage may inhibit thyroid carcinogeneisis in rats, although contributions of other factors, such as a direct inhibitory effect of IM to thyroid follicular cell proliferation cannot be ruled out.

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Formation of refractory ring-expanded triazine intermediates during the photocatalyzed mineralization of the endocrine disruptor amitrole and related triazole derivatives at UV-irradiated TiO2/H2O interfaces.

Amitrole (ATz, 3-amino-1H-1,2,4-triazole) is a widely employed herbicide with strong estrogenic activity that can lead to abnormalities of the thyroid gland and can cause mutations. The photocatalytic transformation of ATz was carried out at the UV-irradiated TiO2/H2O interface, along with the triazole derivatives Tz (1H-1,2,4-triazole) and DaTz (3,5-diamino-1H-1,2,4-triazole) to assess the decomposition of these herbicides, to identify intermediates, and to elucidate some mechanistic details of the ATz degradation. Conversion of the nitrogens of these triazoles to NH4+ and/ or NO3- ions occurs competitively and depends on the number of amine functions on the five-membered triazole rings. Photomineralization of the substrates in terms of loss of nitrogen to NH4+/NO3- was rather low (ca. 25-40%) for each of the triazoles, whereas evolution of CO2 (loss of TOC) was more significant (60-70%), indicating considerable retention of nitrogen in the intermediate products. UV-Vis spectroscopy, TOC assays, FT-IR spectroscopy, proton NMR spectrometry, electrospray LC-MS, and molecular orbital calculations were brought to bear in assessing the temporal course of the photocatalyzed process(es). Results show that after cleavage of the triazole ring, the various intermediate fragments recombine to yield ring-expanded six-membered triazine intermediates, which slowly degrade to give the refractory cyanuric acid under the conditions used.

Amitrole↗