Dimethylaminoazobenzene, carcinogenicity

Brown EV, Coleman RL. 1973. Carcinogenic activity of benzofuran and dibenzofuran analogs of p-dimethylaminoazobenzene. J Med Chem 16 717-718. 

Conversely, he observed that vitamin B 2 may serve to enhance the carcinogenic effect of p-dimethylaminoazobenzene in rats fed a methionine-deficient diet. It is important to note, however, that this was only true in rats on a methionine-deficient diet. 

We have not pursued mechanisms but suggest that the enhancement of carcinogenesis may be related to a role for riboflavin in the activation of enzymatic processes involved with metabolic detoxification of MBN, similar to azo reductase and its role in the detoxification of 4-dimethylaminoazobenzene (32). In this case riboflavin activates azo reductase in the liver and this, in turn, is associated with decreased carcinogenicity. Conversely, when animals are deprived of riboflavin, there is less active enzyme present to detoxify the chemical and the induction of liver cancer is enhanced. A similar process may be functioning in our MBN, riboflavin deprived model but the exact nature of the mechanism requires additional research. 

Early in the twentieth century a very hazardous chemical was used as a food colourant 4-dimethylaminoazobenzene, so-called butter yellow , was a yellow azo dye used in some countries to colour butter, before extensive testing was required. When it was studied in 1947, the dye was shown to be a potent carcinogen capable of causing liver tumours in experimental animals, and it was rapidly withdrawn. Fortunately, the treatment of food with additives, which has now become more extensive, is now safe. 

OSHA PEL Cancer Suspect Agent NIOSH REL (4-Dimethylaminoazobenzene) TWA use 29 CFR 1910.1015 SAFETY PROFILE Confirmed carcinogen with experimental carcinogenic, neoplastigenic, and tumorigenic data. Poison by ingestion and intraperitoneal routes. Experimental teratogenic and reproductive effects. Human mutation data reported. When heated to decomposition it emits toxic fumes of NOx. 

Oral administration of dimethylaminoazobenzene has been shown to produce liver cancer in rats and bladder tumors in dogs. Carcinogenic effects have also been produced following dermal and subcutaneous applications in rats and mice. Dimethylaminoazobenzene is also a teratogen. 

Dimethylaminoazobenzene is listed as a hazardous air pollutant under the Clean Air Act and, when released to the environment, is a hazardous waste. The US Environmental Protection Agency has classified dimethylaminoazobenzene as a probable human carcinogen. This classification is based on the fact that, although there is no epidemiological evidence that links dimethylaminoazobenzene exposure to the development of human cancer, there is sufficient evidence from laboratory animal studies. 

National Institute for Occupational Safety and Health considers 4-dimethylaminoazobenzene to be a potential occupational carcinogen. Special precautions must be taken when working with dimethylaminoazobenzene. Persoimel handling dimethylaminoazobenzene must follow industrial hygiene and health... 

Ketterer, B., Ross-Mansell, P., and Whitehead, J. K., The isolation of carcinogen-binding protein from livers of rats given 4-dimethylaminoazobenzene. Biochem. J. 103, 316-324 (1967). 

When various spices were screened for their ability to potentiate the typical carcinogen-detoxifying enzyme GST in Swiss mice, cumin seeds (Cuminum cyminum Linn.), basil leaves (Ocimum sanctum Linn.), and turmeric increased the enzyme activity by more than 78% in the stomach, liver, and esophagus. GSH levels were also significantly elevated in all three organs by these plant products. These spices also significantly suppressed the chromosome aberrations caused by BaP in mouse bone-marrow cells. In a subsequent study, cumin seeds and basil leaves significantly decreased the incidence of both BaP-induced squamous cell carcinomas in the stomach of Swiss mice and 3 -methyl-4-dimethylaminoazobenzene-induced hepatomas in Wistar rats. ... 

All glycolytic enzymes are increased in amount during carcinogenesis (37, 346). Glucokinase is increased to 570% of its control value in the liver of animals exposed to the carcinogen 3 -methyl-4-dimethylaminoazobenzene (12). 

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