Disease relevance of Methachlor

• Moreover, expression of one of these clones in E. coli resulted in a GST activity as measured with both CDNB and alachlor, proving that at least one of the clones encodes an active GST III species [1].
• The risks of leukemia (rate ratio = 2.83, 95% confidence interval: 0.74, 10.9) and multiple myeloma (rate ratio = 5.66, 95% confidence interval: 0.70, 45.7) were increased among applicators in the highest alachlor exposure category [2].
• When pre-incubated with an olfactory mucosal S9 activation system, alachlor induced a weak, dose-dependent mutagenic response at 500-1250 micrograms/plate, with toxicity at higher doses [3].
• Morphological and phylogenetic analysis enabled the assignment of the alachlor-degrading strains to the genus Streptomyces [4].
• Isolation and characterization of alachlor-degrading actinomycetes from soil [4].

High impact information on Methachlor

• Extracts of Escherichia coli cells expressing SBP1 have strong [3H]Saf binding, which, like binding to the native maize protein, is competitively inhibited by the safener dichlormid and the herbicides S-ethyl dipropylthiocarbamate, alachlor, and metolachlor [5].
• The complete separation of the three compound classes allowed the analysis of the neutral PCs (acetochlor, alachlor, and metolachlor) and their methylated OXA metabolites by gas chromatography/mass spectrometry [6].
• Three different sites of alachlor binding are observed in the BSA system [7].
• Trp12 and Ile118 do not seem to carry out such functions but instead, regulate the K(m) for alachlor by contributing to its productive orientation in the H-site [8].
• Three residues of GST I (Trp12, Phe35 and Ile118), which build up the xenobiotic binding site, were mutated and their functional and structural roles during alachlor conjugation were investigated [8].

Chemical compound and disease context of Methachlor

• The herbicide acetochlor, and its analogue alachlor, have similar toxicological properties, the most significant being the induction of nasal adenomas in rats in 2-year feeding studies [9].
• Klebsiella planticola strain DSZ1 has the ability to degrade different aromatic compounds such as benzoate and organochlorinated as propachlor and alachlor [10].
• DEX pretreatment (25muM, 48h) significantly increased CYP3A7-catalyzed luciferin 6' benzylether O-debenzylation, but had no effect on alachlor toxicity [11].
• Alachlor is cytotoxic to human hepatoblastoma HepG2s, a cell line that expresses constitutive CYP3A7 and dexamethasone (DEX)-inducible CYP3A4 and CYP3A7 [11].
• Using the Microtox method of toxicity assessment designed by Microbics Corporation, the relative toxicities of alachlor, atrazine, and carbofuran, three pesticides commonly used in agricultural production, were determined [12].

Biological context of Methachlor

• Dietary exposure to alachlor depletes olfactory mucosa antioxidants, which may contribute to DNA damage and tissue-specific tumor formation [13].
• Subsequent studies have shown that specific metabolic activation of alachlor is required for nasal tumor formation, and that non-genotoxic, threshold-sensitive processes produce all three tumors [14].
• The effect of vehicle dilution on the percutaneous absorption of alachlor, 2-chloro-2',6'-diethyl-N-(methoxymethyl)acetanilide, through excised human skin was determined using flowthrough design glass penetration cells and 14C radiotracer methodology [15].
• Influence of surface composition on the kinetics of alachlor reduction by iron pyrite [16].
• Cytogenetic effects of alachlor and mancozeb [17].

Anatomical context of Methachlor

• These herbicides are carcinogenic in rats: acetochlor and alachlor cause tumors in the nasal turbinates, butachlor causes stomach tumors, and metolachlor causes liver tumors [18].
• We show here that alachlor rapidly accumulates as GS-conjugates in the plant vacuole and that the first step of its degradation, the formation of the respective gamma-glutamylcysteinyl-S-conjugate, is catalyzed by a vacuolar carboxypeptidase [19].
• Missing Link?: Alachlor and Semen Quality [20].
• In addition, ESA did not elicit the characteristic preneoplastic changes observed in the development of alachlor-induced nasal, stomach, and thyroid tumors [14].
• Both isolated and whole blood human lymphocytes were exposed to alachlor using several protocols [21].

Associations of Methachlor with other chemical compounds

• Cross-polarization magic-angle spinning (CPMAS) 13C NMR spectroscopy has been used to characterize covalent conjugates of alachlor, an alpha-chloroacetamide hapten, with glutathione (GSH) and bovine serum albumin (BSA) [7].
• Pesticide metabolite levels were elevated in Missouri cases, compared with controls, for the herbicides alachlor and atrazine and for the insecticide diazinon [2-isopropoxy-4-methyl-pyrimidinol (IMPY)]; for Wilcoxon rank test, p = 0.0007, 0.012, and 0.0004 for alachlor, atrazine, and IMPY, respectively [22].
• Male Long-Evans rats were fed alachlor for up to 10 days (10-126 mg/kg per day), and intracellular reduced GSH and ascorbate levels were measured in olfactory mucosa [13].
• Biodegradation of the acetanilide herbicides alachlor, metolachlor, and propachlor [23].
• Genotoxicity of humic acid in cultured human lymphocytes and its interaction with the herbicides alachlor and maleic hydrazide [24].

Gene context of Methachlor

• CYP3A4 activity of DPX-2 cells treated with RIF (10muM, 48h) was twice that of untreated cells, but RIF did not increase alachlor toxicity [11].
• Furthermore, immunoblotting showed that alachlor significantly increased CYP2B1/2 and CYP1A1/2 protein levels by 4.2-6.3- and 1.8-fold, respectively [25].
• Zineb and alachlor, on the other hand, enhanced LPS-induced TNF-alpha production by mouse peritoneal macrophages ex vivo, while alachlor inhibited LPS/interferon-gamma-induced NO production ex vivo [26].
• These results suggest that alachlor selectively induces cytochrome P450 isoforms of the CYP1A and CYP2B subfamilies in rat liver microsomes, and that the expression of these isoforms is closely related to the toxicity of alachlor [25].
• The cytotoxicity of 20-65 microg/ml alachlor and 10-65 microg/ml acetochlor was significantly decreased by the addition of 10 microM RESV in Vero ER- cells whereas no significant change was detected on ER+ cell lines MCF-7 and HepG2 [27].

Analytical, diagnostic and therapeutic context of Methachlor

• On-line solid-phase extraction liquid chromatography in combination with mass spectrometry (MS), i.e. MS/MS and orthogonal-acceleration time-of-flight MS, was used for the characterization of photodegradation products of alachlor in river water [28].
• For vegetable samples, alachlor was extracted directly with MeOH and the extracts diluted 1:40 (v/v) with saline buffer prior to ELISA [29].
• HPLC analysis of the alachlor residues in the 2 soils showed that they have a different capacity for absorbing the herbicide, which would account for the different genotoxic responses observed [30].
• Whole body autoradiographic analysis demonstrated localization of radioactivity in the rat nasal tissue following oral administration of alachlor [31].
• The genotoxicity of the herbicides, alachlor, atrazine, maleic hydrazide, paraquat and trifluralin has been evaluated in the single-cell gel electrophoresis (SCGE) assay by using human peripheral blood lymphocytes [32].

References