Disease relevance of NSC 407609

• The environmental contaminant 6-nitrochrysene (6-NC) has been shown to induce adenomas and adenocarcinomas in the colons of rats [1].
• Induction of colon adenocarcinomas in CD rats and lung adenomas in ICR mice by 6-nitrochrysene: comparison of carcinogenicity and aryl hydrocarbon hydroxylase induction in the target organs of each species [2].
• The mutagenic activities in Salmonella typhimurium and tumorigenic activities in newborn mice of 6-nitrochrysene (6-NC), 5-methyl-6-nitrochrysene (5-Me-6-NC), 11-methyl-6-nitrochrysene (11-Me-6-NC) and 5-methylchrysene (5-MeC) were compared [3].
• In the 6NC-treated group, forestomach papillomas and squamous cell carcinomas were also observed in both male (25 and 50%) and female (56 and 33%) transgenic mice [4].
• Induction of cytochrome P450 1A1 in human hepatoma HepG2 cells by 6-nitrochrysene [5].

High impact information on NSC 407609

• Roles of human hepatic and pulmonary cytochrome P450 enzymes in the metabolism of the environmental carcinogen 6-nitrochrysene [6].
• Following the incubations of 6-nitrochrysene with 11 different human pulmonary microsomes, qualitatively similar metabolic patterns were obtained, although quantitative differences were evident [6].
• In an attempt to define the roles of individual human hepatic P450 involved in the metabolism of 6-nitrochrysene, the catalytic activities known to be associated with a specific P450 were analyzed and compared with the levels of each metabolite of 6-nitrochrysene formed with the same microsomes [6].
• Species and organ specificity of 6-nitrochrysene (6-NC)-induced carcinogenicity and the potential correlation with aryl hydrocarbon hydroxylase (AHH) induction in the target organs were investigated in both sexes of ICR mice and CD rats [2].
• The influence of induction of drug metabolizing enzymes on the activation pathway of 6-nitrochrysene in an intact cell system was tested using rat hepatocytes [7].

Biological context of NSC 407609

• Metabolic activation of 6-nitrochrysene in explants of human bronchus and in isolated rat hepatocytes [7].
• These results were compared to ploidy data from primary MGTs induced by two synthetic carcinogens, 7,12-dimethylbenz[a]antracene and nitrosomethylurea in female Brown Lewis Norway rats and an environmental carcinogen, 6-nitrochrysene, in female Sprague-Dawley rats [8].

Anatomical context of NSC 407609

• Metabolism and DNA binding of the environmental pollutant 6-nitrochrysene in primary culture of human breast cells and in cultured MCF-10A, MCF-7 and MDA-MB-435s cell lines [9].
• Comparative tumorigenicity of the environmental pollutant 6-nitrochrysene and its metabolites in the rat mammary gland [10].
• The results indicate that 6-nitrochrysene, 6-aminochrysene and their metabolites are mutagenic in CHO cells, but that the major activation pathway for 6-nitrochrysene and 6-nitrochrysene-1,2-dihydrodiol in this system differs from previously described pathways [11].

Associations of NSC 407609 with other chemical compounds

• Mutagen-DNA adducts were analyzed by 32P-postlabeling in cells treated under the conditions of the mutagenicity assay and compared with the adduct patterns produced from the in vitro reaction of metabolites of 6-nitrochrysene and 6-aminochrysene with calf-thymus DNA [11].

Gene context of NSC 407609

• 6-Nitrochrysene can be activated by human P450 1A2 but the (mono) nitropyrenes examined were not; these were oxidized by P450 3A4 instead [12].
• Relationships of DNA adduct formation, K-ras activating mutations and tumorigenic activities of 6-nitrochrysene and its metabolites in the lungs of CD-1 mice [13].
• The present study has determined the effects of 6-nitrochrysene (6-NC) on human cytochrome P450-dependent monooxygenases in human hepatoma HepG2 cells [5].

Analytical, diagnostic and therapeutic context of NSC 407609

• A newborn mouse (BLU:Ha) lung adenoma bioassay demonstrated that 6-nitrochrysene was a highly potent tumorigen [14].
• Caloric restriction profoundly inhibits liver tumor formation after initiation by 6-nitrochrysene in male mice [15].
• Administration of 100 nmol/mouse of 6-nitrochrysene, only on day 1, caused about the same tumor yield as was observed after treatment with 700 nmol/mouse given over 3 days [16].
• The remarkable carcinogenic activity of 6-nitrochrysene (6-NC) in several animal models, and its environmental presence, suggest its potential importance with regard to human cancer development [17].
• Therefore, one of the goals of this study was to determine the propensity of the environmental contaminant 6-nitrochrysene (6-NC) for inducing mammary cancer following its oral administration to female CD rats [10].

References