Disease relevance of Casoron gsr

• The herbicide 2,6-dichlorobenzonitrile (DCBN) is known to cause tissue-specific toxicity at very low doses in the olfactory mucosa of rodents [1].
• Further experiments showed that there was no evidence for a binding of [14C]dichlobenil metabolites to calf thymus DNA or a formation of mutagenic dichlobenil metabolites in Ames' Salmonella assay when dichlobenil was incubated in the presence of homogenates of the olfactory mucosa [2].
• Production of cellulose II by Acetobacter xylinum in the presence of 2,6-dichlorobenzonitrile [3].
• Dichlobenil induced a significant increase of malignant tumors (lymphoma, mesothelioma, hepatocellular carcinoma, and pulmonary alveologenic carcinoma) with respect to the controls (p less than 0.01 in both treated groups) [4].
• Three and six months after exposure to dichlobenil (2x or 1 x 25 mg/kg i.p.), the dorsomedial part of the olfactory region showed a respiratory metaplasia with abundant invaginations and a fibrotic lamina propria [5].

High impact information on Casoron gsr

• We first transiently disrupted the parallel order of microfibrils in mor1-1 using a brief treatment with the cellulose synthesis inhibitor 2,6-dichlorobenzonitrile (DCB) [6].
• Some cyt1 defects can be partially phenocopied by treatment with the herbicide dichlobenil, which is thought to interfere with cellulose biosynthesis [7].
• Metabolic activation of 2,6-dichlorobenzonitrile, an olfactory-specific toxicant, by rat, rabbit, and human cytochromes P450 [1].
• We found that the chemical dichlobenil can produce specific and permanent ablation of neurons in odorant receptor expression zone 1, while a higher dichlobenil dose causes reversible toxicity in neighboring zones [8].
• Intraperitoneal injections of dichlobenil selectively destroyed the sensory neuroepithelium of the nasal cavity without direct physical insult to the olfactory neuron pathway [9].

Chemical compound and disease context of Casoron gsr

• The metyrapone treatment also resulted in a decreased or completely inhibited toxicity of dichlobenil to the olfactory mucosa [10].
• Treatment with 3-aminobenzamide, known as an inhibitor of poly(ADP-ribose)polymerease, decreased the toxicity and covalent binding of the herbicide dichlobenil (2,6-dichlorobenzonitrile; 12 mg/kg; i.p.) in the mouse olfactory mucosa [2].
• No protective effects of the cyanide antidotes nitrite, thiosulfate, or superoxide dismutase on the dichlobenil-induced toxicity were observed [11].
• The herbicides dichlobenil (2,6-dichlorobenzonitrile) and chlorthiamide (2,6-dichlorothiobenzamide) and the environmental dichlobenil metabolite 2,6-dichlorobenzamide all induce toxicity in the OM following covalent binding in the Bowman's glands [12].
• The results of this study thus show that single doses of DFBN, DFBA, BN, IX and BX, compounds structurally related to the potent olfactory toxicant dichlobenil, do not elicit acute toxicity in the olfactory mucosa of mice [13].

Biological context of Casoron gsr

• The low toxicity of dichlobenil in the postnatal olfactory mucosa, despite a high irreversible binding at this site, may possibly be related to the cell proliferation in the developing olfactory mucosa leading to replacement of damaged cells [14].
• Olfactory mucosal histology revealed that single or multiple exposures to 50, 100, 150 and 200 mg/kg dichlobenil dermally caused olfactory epithelial damage (primarily sensory cell loss) in the epithelium lining the dorsal medial meatus of the nasal cavity [15].
• In conclusion, the results do not support a major role for P4502E1 in the metabolic activation of dichlobenil or hydroxylation of NP in rat olfactory microsomes and suggest that these catalytic activities in the olfactory mucosa may represent a common form of P450 [16].
• Chlorthiamid (IC50 = 51 microM), but not DCBA, inhibited the covalent binding of 14C-labeled dichlobenil in the olfactory mucosa in vitro [17].

Anatomical context of Casoron gsr

• These observations, coupled with the known profile of metabolites for dichlobenil, suggest that systemically-administered compounds causing site-specific lesions in the epithelium lining the DMM of the nasal cavity may do so by the in situ production of reactive epoxide metabolites which are then poorly capable of being detoxified [18].
• Physiological and histological recovery of the olfactory mucosa of the frog after a dichlobenil injection [19].
• In homogenates of the olfactory mucosa (mouse 1000 x g supernatants; rat microsomes), dichlobenil was metabolized and covalently bound to protein [20].
• The NP-hydroxylation in olfactory microsomes was > 6 times higher than that in liver microsomes and was markedly decreased following addition of dichlobenil, DEDTC or metyrapone [16].

Associations of Casoron gsr with other chemical compounds

• This study represents part an of ongoing effort to understand the mechanism underlying the distribution of the olfactory mucosal lesion resulting from the systemic administration of compounds such as 2,6-dichlorobenzonitrile (dichlobenil) and beta,beta'-iminodipropionitrile (IDPN) [18].
• The cellulose biosynthesis inhibitors 2,6-dichlorobenzonitrile and isoxaben both caused dramatic reductions in the number of cells depositing wall ingrowths, altered wall ingrowth morphology and visibly disrupted microfibril structure [21].
• Both the gross and subcellular appearance of P-450 immunoreactivity in metyrapone/dichlobenil treated mice was similar to controls [22].
• This paper presents first experiments of laboratory investigations of the photodegradation by direct photolysis (lambda>290 nm) of cholorotahlonil, dichlobenil, chloroxynil, bromoxynil, and ioxynil in aqueous, pH-buffered, and organic solutions and the calculation of the quantum yields [23].
• Taurine in the olfactory system: effects of the olfactory toxicant dichlobenil [24].

Gene context of Casoron gsr

• The treatment of water frogs with the herbicide dichlobenil decreased both the above-mentioned activities and the immunoreactive CYP2A apoprotein [25].
• We used DDTC in order to examine the role that cytochrome P450 2E1 plays in the bioactivation of beta,beta'-iminodipropionitrile (IDPN) and 2,6-dichlorobenzonitrile (dichlobenil), resulting in site-specific olfactory lesions in the Long-Evans rat and C57B1 mouse [26].
• In conclusion, the results demonstrate a relationship between the degrees of covalent binding, GSH depletion, and toxicity of dichlobenil in the olfactory mucosa [11].
• 3-Aminobenzamide: effects on cytochrome P450-dependent metabolism of chemicals and on the toxicity of dichlobenil in the olfactory mucosa [2].
• Antibodies to cytochromes P-450NMa and P-450NMb (CYP2A and CYP2G1, respectively) (P-450 nomenclature by Nebert et al., DNA Cell Biol. 10, 1- (1-14) 14, 1991) were used to assess the effects of the herbicide dichlobenil on the distribution of these olfactory-specific isozymes in the olfactory mucosa [22].

Analytical, diagnostic and therapeutic context of Casoron gsr

• A quantitative enzyme-linked immunoassay for the detection of 2, 6-dichlorobenzamide (BAM), a degradation product of the herbicide dichlobenil [27].
• The irreversible binding and toxicity of the olfactory toxicant dichlobenil in the mouse perinatal olfactory mucosa were examined by autoradiography and histopathology [14].

References