Nitrosoamines carcinogen

Liver cancer can also be a consequence of exposure to hepatotoxic chemicals. Natural hepatocarcinogens include fungal aflatoxins. Synthetic hepato-carcinogens include nitrosoamines, certain chlorinated hydrocarbons, polychlorinated biphenyls (PCBs), chloroform, carbon tetrachloride, dimethyl-benzanthracene, and vinyl chloride.Table 5.15 lists the chemical compounds that induce liver cancer or cirrhosis in experimental animals or... 

Although chemicals in closed circulation systems do not generally come into contact with the environment - except perhaps on disposal - problems can exist with safety in handling. A particular example is the need for caution in the mixing of coolants containing nitrites with those containing amines because of the possible production of carcinogenic nitrosoamines. This caution has been expressed in other fields of use of inhibitors (see below). 

The function of sodium nitrite, NaN02, as a food additive is two-fold (1) it inhibits the oxidation of blood, preventing the discoloring of red meat, and (2) it prevents the growth of botulism bacteria. There is now some controversy regarding this food additive because nitrites are suspected of combining with amines under the acidic conditions of the stomach to produce carcinogenic nitrosoamines. 

N-nitrosoamines cannot be dissected into active and inactive regions, but they must be considered in their entirety. Therefore, one cannot simply look at the compounds and predict their carcinogenicity because no single region of the structure is responsible for the biological activity [81]. 

Nitrogen species, such as nitrate and nitrite, are known to be confirmed procarcinogens. The excessive input of these nitrogen compounds with food and drinking water in the presence of tertiary amines, for instance, from medicines, can lead to the formation of carcinogenic N-nitrosoamines. 

Westin, J.B., Spiegelhalder, B., Preussmann, R. Shani, J. (1990) Assay of suntan lotions for the carcinogenic, non-volatile V-nitrosoamine V-nitrosodiethanolamine. Cancer Lett., 50, 157-160... 

Some of these nitrosoamines and nitrosoamides are known to be potent carcinogens for some animals, which is reason to suspect they also may be carcinogenic for humans. However, it is clear that there may be very marked differences in carcinogenic properties of a given compound for different animal species. 

CAUTION The intermediate in this reaction, as an N-nitrosoamine, is potentially carcinogenic see Section 2.3.4, p. 49). 

Nitrosoamines (Fig. 7.8) are the most dangerous EDCs, showing several mutagenic and carcinogenic properties [75]. 

The polychlorinated biphenyls occur widely as environmental pollutants and have been observed in the food chain. GC-MS has been applied in various aspects of their analysis (for leading references see [504, 505,513]). In the general area of food chemistry and contamination control, claims for the presence of carcinogenic nitrosamines in foodstuffs have been evaluated by specific GC-MS techniques [514,515]. However, it has been suggested that there may be a current over obsessive interest in the possible hazards of a few ppb of nitrosoamines in food [516]. 

Gruetter, C., Barry, BK, McNamara, DB, Gruetter, DY, Kadowitz, PJ, and Ignarro, L. 1979. Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoamine. J Cyclic Nucleotide Res 5 211-224. 

Reactions of these compounds with the secondary and tertiary amines contained in many foods lead to the known carcinogens. V-nitrosoamines ... 

The brown color of old meat is the result of oxidation of blood and is objectionable to many consumers. Nitrites and nitrates are added to food to retard this oxidation and also to prevent growth of botulism bacteria. Nitrate ions, N03, are reduced to N02 ions, which are then converted to NO. This in turn reacts with the brown oxidized form of the heme in blood. This reaction keeps meat red longer. Controversy has arisen, however, concerning the possibility that nitrites combine with amines under the acidic conditions in the stomach to produce carcinogenic nitrosoamines. 

IARC (International Agency for Research on Cancer). 1982. Laboratory decontamination and destruction of carcinogens in laboratory wastes Some N-nitrosoamines. lARC Scientific Publication No. 43. 

Khudoley V, Malaveille C, Bartsch H. 1981. Mutagenicity studies in Salmonella tvnhimurium on some carcinogenic N-nitrosoamines in vitro and in the host-mediated assay in rats. Cancer Res 41 3205-3210. 

N2O3 formed by a third order reaction, can deaminate DNA bases yielding uracil from cytosine, xanthine from guanine, methyl cytosine from thymine and hypoxanthine from adenine [ 56 ]. Furthermore, it can react with secondary amines to yield carcinogenic N-nitrosoamines, which can damage DNA by alkylation, [57]. 

A U. S. National Research Council report concludes that natural and synthetic carcinogens are present in human foods at such low levels that they pose little threat.42 It points out that consuming too many calories as fat, protein, carbohydrates, or ethanol is far more likely to cause cancer than consuming the synthetic or natural chemicals in the diet. However, it also mentions several natural substances linked to increased cancer risk heterocyclic amines formed in the overcooking of meat nitrosoamines, aflatoxins, and other mycotoxins.43 Typical of the heterocyclic amine mutagens are compounds 1.9 and 1.10, the first from fried beef and the second from broiled fish 44... 

N-nitroso compounds (nitrosoamines) are characterized by the -N -N = O functional group. They are monitored in many materials to which human beings may be exposed, like whiskey, beer and cutting oil used in machining. Dimethylnitro so amine, (CH3)2N-N = 0, once widely used as an industrial solvent, was shown to be carcinogenic. These nitrosoamines are formed also in the body when uptake of excessive nitrates is accompanied with some drugs containing secondary amines (see Chapter 13 also). 

Furthermore, nitrites formed by the reduction of nitrates can react with secondary amines in the gastrointestinal tract to produce potentially carcinogenic nitrosoamines. 

Group II contains the strong carcinogens — substances inducing tumours in a fairly short time in most laboratory animals, the carcinogenic effect on the man being probable (e.g. aminoazo compounds, nitrosoamines). 

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