Disease relevance of o-Methylnitrobenzene

• o-Nitrotoluene-induced large intestinal tumors in B6C3F1 mice model human colon cancer in their molecular pathogenesis [1].
• These alterations, which are hallmarks of human colon cancer, probably contributed to the pathogenesis of the large intestinal carcinomas in mice following o-nitrotoluene exposure [1].
• Cloning and sequencing of the genes encoding 2-nitrotoluene dioxygenase from Pseudomonas sp. JS42 [2].
• The protein components of the 2-nitrotoluene (2NT) and nitrobenzene dioxygenase enzyme systems from Acidovorax sp. strain JS42 and Comamonas sp. strain JS765, respectively, were purified and characterized [3].
• The most prominent neoplastic lesions in mice in the 2-year studies of o-nitrotoluene and riddelliine were hemangiosarcomas [4].

High impact information on o-Methylnitrobenzene

• When F344 females with conventional intestinal microflora were gavaged with 2NT and primary hepatocyte cultures were prepared, no unscheduled DNA synthesis was observed (200 mg/kg: -2.6 NG) [5].
• 2NT did not induce DNA repair in germ-free animals (200 mg/kg: -3.8 NG), whereas DNA repair was induced in Charles River Altered Schaedler Flora-associated animals (200 mg/kg: 5.4 NG) [5].
• These results demonstrate that the mononitrotoluenes display marked isomeric differences in their genotoxic potential, indicate the obligatory role of intestinal bacteria in the metabolic activation of 2NT, and show that the genotoxic potential of 2NT is dependent upon the sex of the animal under study [5].
• Twenty-four hr following treatment with 2NT, a 50-fold increase in the number of hepatocytes in S phase was observed and indicated that 2NT induces cell division in addition to DNA repair [5].
• The recently completed o-nitrotoluene study provided the first cecal tumor response and an opportunity to evaluate the morphology and molecular profile of oncogenes and tumor suppressor genes that are relevant to humans [1].

Chemical compound and disease context of o-Methylnitrobenzene

• A strain of Pseudomonas sp. was isolated from nitrobenzene-contaminated soil and groundwater on 2-nitrotoluene as the sole source of carbon, energy, and nitrogen [6].
• Oxidative release of nitrite from 2-nitrotoluene by a three-component enzyme system from Pseudomonas sp. strain JS42 [7].
• Sequence analysis showed that the components of NBDO have a high level of homology with the naphthalene family of Rieske nonheme iron oxygenases, in particular, 2-nitrotoluene dioxygenase from Pseudomonas sp. strain JS42 [8].

Biological context of o-Methylnitrobenzene

• Greater flexibility with respect to the introduction of nuclear substituents was achieved by conversion of 2-nitrotoluene derivatives to 2 via acylation of intermediate beta-(dimethylamino)-2-nitrostyrenes with various aroyl chlorides and hydrolysis [9].
• A computational study on the kinetics and mechanism for the unimolecular decomposition of o-nitrotoluene [10].
• This study was performed to characterize the gene expression profile and to identify the major carcinogenic pathways involved in rat peritoneal mesothelioma (RPM) formation following treatment of Fischer 344 rats with o-nitrotoluene (o-NT) or bromochloracetic acid (BCA) [11].
• Mutations in at least one of these genes were identified in 13 of 15 (87%) of the o-nitrotoluene-induced hemangiosarcomas with missense mutations in p53 exons 5-8 detected in 11 of 15 (73%) of these neoplasms [4].
• Active site residues controlling substrate specificity in 2-nitrotoluene dioxygenase from Acidovorax sp. strain JS42 [12].

Anatomical context of o-Methylnitrobenzene

• In contrast to the o-nitrotoluene study, 7/12 (58%) riddelliine-induced hemangiosarcomas had K-ras codon 12 GTT mutations and, when screened by immunohistochemistry, 9/12 (75%) had strong staining for the p53 protein in malignant endothelial cells, the cells of origin of hemangiosarcomas [4].
• Fifteen o-nitrotoluene-induced hemangiosarcomas of the skeletal muscle, subcutaneous tissue, and mesentery; 12 riddelliine-induced hemangiosarcomas of the liver; and 15 spontaneous subcutaneous hemangiosarcomas were examined for genetic alterations in ras, p53, and beta-catenin genes [4].
• By 2 years, mesotheliomas, skin, liver, mammary gland and liver tumors also occurred in 'stop-study' male rats that received o-nitrotoluene at 125 or 315 mg/kg per day for only the first 3 months of study [13].

Associations of o-Methylnitrobenzene with other chemical compounds

• Purification, characterization, and crystallization of the components of the nitrobenzene and 2-nitrotoluene dioxygenase enzyme systems [3].
• Nitrotoluenes, such as 2-nitrotoluene, 2,4-dinitrotoluene (24DNT), and 26DNT, are carcinogenic in animal experiments [14].

Gene context of o-Methylnitrobenzene

• Chemical-specific alterations in ras, p53, and beta-catenin genes in hemangiosarcomas from B6C3F1 mice exposed to o-nitrotoluene or riddelliine for 2 years [4].
• The kinetics and mechanism for the unimolecular decomposition of o-nitrotoluene (o-CH(3)C(6)H(4)NO(2)) have been studied computationally at the G2M(RCC, MP2)//B3LYP/6-311G(d, p) level of theory in conjunction with rate constant predictions with RRKM and TST calculations [10].
• Air concentrations of DNT and 2NT did not correlate with the levels of metabolites in the urine [15].
• The only histopathologic evidence for treatment-related toxicity in mice in the 13-week studies occurred in animals receiving the o-nitrotoluene isomer where the chemical caused degeneration and metaplasia of the olfactory epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)[16]
• Evidence of liver toxicity in the male rats receiving o-nitrotoluene included hepatocyte vacuolization, oval cell hyperplasia, and increased serum bile acids, sorbitol dehydrogenase, and alanine aminotransferase [16].

Analytical, diagnostic and therapeutic context of o-Methylnitrobenzene

• Only 2NT at 12 hr after treatment induced DNA repair (200 mg/kg: 15.4 NG) [5].
• The construction and some analytical applications of a liquid picrolonate (Picrl-) ion-selective electrode based on the tris(phenanthrolinato)iron(II) (ferroin) picrolonate salt, dissolved in 2-nitrotoluene, are described [17].

References