Disease relevance of Hexametapol

• The replication of Sarcoma 180 cells in culture was inhibited by 3,6-dihydroxy-4,5-dimethylphthalaldehyde (HMPA) [1].
• Rhinitis also was increased in severity by HMPA in conventional rats, but not in experimentally infected PF or axenic rats [2].
• Severity of otitis media and tracheitis was not affected by HMPA [2].
• In the absence of M. pulmonis infection, HMPA treatment of rats caused thinning and microulceration of respiratory epithelium in major bronchi without inflammatory lung disease [2].
• Rats exposed by inhalation to hexamethylphosphoramide (HMPA) at concentrations of 50, 100, 400, and 4000 parts per billion (ppb) for 6-24 months revealed nasal tumors and squamous metaplasia with inflammation in the nasal epithelium, but no changes were observed at 10 ppb [3].

High impact information on Hexametapol

• Induction of nasal tumors in rats exposed to hexamethylphosphoramide by inhalation [4].
• Other effects induced by HMPA, with or without the infection, were destruction and fibrous replacement of olfactory epithelium, atrophy of testes, and reduced weight gains [2].
• HMPA acts as a catalyst for the ortho-to-benzylic translocation and anionic cyclization reactions [5].
• In addition, evidence is provided that NMa is the major catalyst in the dealkylation of two nasal carcinogens, hexamethylphosphoramide and phenacetin, in both olfactory and respiratory nasal microsomes [6].
• The cross-linking agent hexamethylphosphoramide predominantly induces intra-locus and multi-locus deletions in postmeiotic germ cells of Drosophila [7].

Chemical compound and disease context of Hexametapol

• However, both enzymes were active in the metabolic activation of hexamethylphosphoramide, a nasal procarcinogen, and 2,6-dichlorobenzonitrile (DCBN), a herbicide known to cause tissue-specific toxicity in the olfactory mucosa of rodents at very low doses [8].
• The absorption spectrum of the hydrogenase from Chromatium, which contains four iron atoms and four atoms of acid-labile sulfide, in 80% dimethylsulfoxide or hexamethylphosphoramide suggests the presence of a single [4Fe-4S] cluster [9].

Biological context of Hexametapol

• HMPA was injected immediately after arising from a supine position [10].
• The rate of hydrolysis to formaldehyde of methylenedimorpholine (MDM), hexamethylenetetramine (HMT) and dinitrosopentamethylenetetramine (DNPT) have been compared with the enzyme-mediated formation of formaldehyde from hexamethylphosphoramide (HMPA) [11].
• Thus, in genetic terms, as most potent carcinogens in rodents appear to be those agents giving no effect or a low activity in the exr- genotype in Drosophila: carcinogens with high potential for direct miscoding [ENU, ENNG, DEN, iPMS, CEO and presumably DMBA (?)], and those capable of forming crosslinks (MC, MCT, HMPA, Thio-TEPA and BCNU) [12].
• The nature of DNA sequence changes induced by the cross-linking agent hexamethylphosphoramide (HMPA) within and in the vicinity of the vermilion locus of Drosophila melanogaster that produce a vermilion mutant phenotype was analyzed after exposure of postmeiotic male germ cells [7].
• The synthetic strategy applied to prepare bisindene 5 relies on the efficient alkylation of 2-(phenylsulfonyl)indane followed by HMPA-assisted E1cB-elimination of phenylsulfinate [13].

Anatomical context of Hexametapol

• The ciliated cells of the airway epithelium were denuded, and microulcerative lesions in the epithelium were induced in the HMPA-treated rats [14].
• Significant dose-dependent increases in DPXL formation were observed in respiratory and olfactory epithelial cells exposed to > or = 0.5 and 1 mM HMPA, respectively, for 3 h at 37 degrees C. This resulted in DPXL accumulation at 18-20% higher levels than untreated cells [15].
• Both test chemicals produced a statistically significant increase (P 0.001) in the incidence of micronuclei in bone marrow cells in all strains at both sampling times but the response with HMPA in C57Bl/6J mice appears to occur earlier than in the other two strains [16].
• Hexamethylphosphoramide (HMPA) is a rat nasal carcinogen that induces squamous cell carcinomas in the anterior portions of the nasal cavity following chronic inhalation exposures as low as 50 ppb [17].
• Using a filter binding assay, we demonstrated that microsomal activation is necessary for HMPA-induced crosslink formation between plasmid DNA and calf thymus histones, presumably through metabolic N-demethylation of HMPA and the formation of formaldehyde [15].

Associations of Hexametapol with other chemical compounds

• Rearrangements, mostly deletions, represented by far the most frequent type of mutational events induced by HMPA that are detected as vermilion mutations [7].
• They provided lower frep-/frep+ indices than would be anticipated on the basis of their nucleophilic selectivity (MC, BCNU, Thio-TEPA) or were even inactive (FA, MCT, HMPA) in the Drosophila repair assay [12].
• 3. The Fe-S core of component C was extruded by treating the protein with p-methoxybenzenethiol in hexamethyl phosphoramide/50mM-Tris/HCl buffer, pH 8.5 (4:1, v/v), under anaerobic conditions [18].
• The reaction of fluorobenzene with Me3Si- anion (1) in HMPA at room temperature surprisingly affords o- and p-fluorotrimethylsilylbenzenes (substitution of aromatic H for TMS, 76% yield) 7a and 7b and also 14% of trimethylsilylbenzene (2) [19].
• The response of 3 strains of mouse (C57Bl/6J, C3H/C57 hybrid and BALBC/CBA) to cyclophosphamide (75 mg/kg) and hexamethylphosphoramide (HMPA) (1.28 ml/kg) were compared in the micronucleus test [16].

Gene context of Hexametapol

• Hexamethylphosphoric triamide as a solubilizing agent. Purification and reactivation of diglyceride kinase [20].
• Nasal cytochrome P450 2A: identification, regional localization, and metabolic activity toward hexamethylphosphoramide, a known nasal carcinogen [21].
• Fmoc-amino acids were anchored to aminopropyl Perloza beaded cellulose via the TFA labile 4-oxymethylphenoxyacetyl (HMPA) linker [22].

Analytical, diagnostic and therapeutic context of Hexametapol

• The inhibition of growth caused by HMPA was evident after treatment of cells with drug for only 15 min [1].
• Selection of an in vitro carcinogenicity test for derivatives of the carcinogen hexamethylphosphoramide [23].
• Gel filtration of protected peptides on sephadex G-50 in hexamethylphosphoramide containing 5% water [24].
• A hexamethylphosphoric triamide proved to be a useful solvent for negative ion fast atom bombardment mass spectrometry (FABMS) of underivatized gangliosides, using a conventional glycerol matrix [25].
• The HMPA proved to be as reliable and specific as the conventional PCR technique [26].

References