Disease relevance of DINITROTOLUENE

• Dinitrotoluene: acute toxicity, oncogenicity, genotoxicity, and metabolism [1].
• Technical grade dinitrotoluene (TDNT), composed principally of 2,4-DNT (76%) and 2,6-DNT (20%), is a potent hepatocarcinogen when fed to male F-344 rats for 1 year (100% incidence of hepatocellular carcinoma) while 2,4-DNT is only weakly hepatocarcinogenic [2].
• The genes encoding the degradative pathway were identified within a 27-kb region of DNA cloned from Burkholderia cepacia R34, a strain that grows using 2,4-DNT as a sole carbon, energy, and nitrogen source [3].
• Cloning and characterization of Pseudomonas sp. strain DNT genes for 2,4-dinitrotoluene degradation [4].
• The frequency of chromosomal aberrations (gaps included) was increased (P < 0.05) in the exposed workers in comparison with a group of factory controls and correlated with the level of 24DNT Hb-adducts in young subjects (<31 years) [5].

High impact information on DINITROTOLUENE

• The hepatocarcinogenicity of 2,4-dinitrotoluene [(2,4-DNT) CAS: 121-14-2], 2,6-DNT (CAS: 606-20-2), and a representative technical-grade DNT (TDNT) containing 76% 2,4-DNT and 18% 2,6-DNT was studied in male F344 rats [6].
• For example, Phanerochaete chrysosporium mineralizes 2,4-dinitrotoluene and 2,4,6-trinitrotoluene and shows promise as the basis for bioremediation strategies [7].
• Hydrolysis of Hb from rats dosed with 24DNT yields, 4-amino-2-nitrotoluene (4A2NT) (16.3 nmol/g Hb), 24TDA (4.3 nmol/g Hb) and 4-acetylamino-2-aminotoluene (4AA2AT) (0.51 nmol/g Hb) [8].
• The method was validated by controlled exposure of the membranes to standard gaseous mixtures of 2,4,6-trinitrotoluene (TNT) and 2,4-dinitrotoluene (2,4-DNT) [9].
• The kinetics of the catalytic reaction between the biosensor and TNT and 2,4-dinitrotoluene (DNT) were characterized using rotated disk electrode and cyclic voltammetry techniques, and values of 1.4 x 10(4) and 7.1 x 10(4) M(-1) s(-1) were obtained for TNT and DNT, respectively [10].

Chemical compound and disease context of DINITROTOLUENE

• The degradation of 2,4-dinitrotoluene (DNT) by Pseudomonas sp. strain DNT is initiated by a dioxygenase attack to yield 4-methyl-5-nitrocatechol (MNC) and nitrite [4].
• Pseudomonas sp. strain DNT degrades 2,4-dinitrotoluene (DNT) by a dioxygenase attack at the 4,5 position with concomitant removal of the nitro group to yield 4-methyl-5-nitrocatechol (MNC) [11].
• Saturation mutagenesis of Burkholderia cepacia R34 2,4-dinitrotoluene dioxygenase at DntAc valine 350 for synthesizing nitrohydroquinone, methylhydroquinone, and methoxyhydroquinone [12].
• 4-Methyl-5-nitrocatechol (4M5NC) monooxygenase (DntB) from Burkholderia sp. strain DNT catalyzes the second step of 2,4-dinitrotoluene degradation by converting 4M5NC to 2-hydroxy-5-methylquinone with the concomitant removal of the nitro group [13].
• The products detected in the incubation of 2,4-dinitrotoluene (2,4-DNT) with Salmonella typhimurium strains TA98 and TA98/1,8-DNP6 were nitrosonitrotoluenes, hydroxylaminonitrotoluenes, aminonitrotoluenes and dimethyl dinitroazoxybenzene [14].

Biological context of DINITROTOLUENE

• Identification of biotransformation products from 2,4-dinitrotoluene [15].
• No sex differences in the hepatic macromolecular covalent binding were observed after perfusion of livers with either 20 or 70 micro M 2,4-DNT [16].
• Nevertheless, loss of the 2,4-dinitrotoluene degradative phenotype was observed for strains carrying pJS1 [17].
• Livers from both sexes displayed a capacity for oxidation, reduction, acetylation and conjugation of 2,4-DNT (or its metabolites) [16].
• DNT-induced hepatotoxicity was found to correlate with an inhibition of protein synthesis and an increase in lactate dehydrogenase (LDH) release but not with lipid peroxidation [18].

Anatomical context of DINITROTOLUENE

• Dinitrotoluene structure-dependent initiation of hepatocytes in vivo [2].
• Metabolism of 2,4-DNT by liver and lung microsomes yielded mainly 2,4-DNBAlc with lower amounts of 4A2NT and 2A4NT, and their formation was dependent on the presence of oxygen and NADPH [19].
• Aerobic metabolism of 2,4-DNT by explants of the small intestine, large intestine, or by cecal contents yielded 2,4-DNBAlc, 2A4NT, 4A2NT and 4-(N-acetyl)amino-2-nitrotoluene (4Ac2NT) [19].
• Reduction of 2,4-dinitrotoluene by Wistar rat liver microsomal and cytosol fractions [20].
• The present study was undertaken to evaluate the effects of the chemosterilant 2,4-dinitrotoluene (DNT) on the rat testis [21].

Associations of DINITROTOLUENE with other chemical compounds

• Following 5 day p.o. treatment of male F-344 rats with aflatoxin B1 (AFB), 2-acetylaminofluorene (AAF), technical grade dinitrotoluene (DNT), or 2,4-diaminotoluene, microsomal cytochrome P450 dependent enzyme activities were depressed while epoxide hydrolase activity was markedly elevated (3-8 times control) [22].
• The inhibition of metabolic cooperation by DMSO, the requirement for only short-lived reductions in metabolic cooperation for maximal TGR cell recovery, and the lack of inhibition by DNT suggests that caution should be exercised when interpreting the results of this bioassay [23].
• The order of potency for increasing epoxide hydrolase was AFB greater than AAF greater than 2,6-dinitrotoluene greater than 3'-methyl-N,N-dimethyl-4-aminoazobenzene greater than DNT greater than 2, 4-dinitrotoluene [22].
• Microcosm studies using a DNT-degrading culture from column effluent suggest that, after the onset of 2,4-DNT degradation, nitrite evolution will eventually control the extent of degradation achieved by two mechanisms [24].
• In column studies conducted at field capacity, high levels of 2,4-DNT biodegradation were rapidly stimulated by the addition of a complete mineral medium but not by bicarbonate-buffered distilled deionized water or by phosphate-amended tap water [24].

Gene context of DINITROTOLUENE

• 4-Methyl-5-nitrocatechol (MNC) is an intermediate in the degradation of 2,4-dinitrotoluene by Burkholderia sp. strain DNT [25].
• MacA was found to be most closely related to TftE, the maleylacetate reductase from Burkholderia cepacia AC1100 (62 % identical positions) and to a presumed maleylacetate reductase from a dinitrotoluene catabolic gene cluster from B. cepacia R34 (61 % identical positions) [26].
• DDO DntAc variant I204L also transformed both 2,6-DNT and 2,4-DNT 2-fold faster than wild-type DDO (0.8 +/- 0.6 nmol/min/mg protein and 4.7 +/- 0.5 nmol/min/mg protein, respectively) [27].
• The most potent inducers of DT-diaphorase activity were 3-methylcholanthrene, polychlorinated biphenyls and dinitrotoluene [28].
• The field samples are analyzed for the presence of explosives, of which DNT and RDX are indeed detected [29].

Analytical, diagnostic and therapeutic context of DINITROTOLUENE

• Technical grade dinitrotoluene (TDNT) was shown to be a potent hepatocarcinogen in rats; however, ambiguous results were obtained from bioassays which evaluated 2,4-DNT, the principal isomer in the technical mixture [30].
• The transport of DNBalcG into the bile of male, but not female, livers appeared to be saturated after perfusion with 20 micro M 2,4-DNT [16].
• We previously reported on the mineralization of 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) in an aerobic fluidized-bed bioreactor (FBBR) (Lendenmann et al. 1998 Environ Sci Technol 32:82-87) [31].
• We present possible modes of action of 2,4-DNT toxicity and suggest that fathead minnow cDNA microarrays can be useful to identify mechanisms of toxicity in fish and as a predictive tool for toxicity in mammals [32].
• After 2,4-DNT and 2,6-DNT applications (acetone and soils), HPLC analysis of radiolabel in receptor fluid during the period of maximum flux revealed no significant metabolites [33].

References