PAHs, carcinogenic

Benzo[ z]pyrene and other Mutagens and PAHs carcinogens... 

Diet is the major source of PAHs to humans. Authorities agree that most foods contain 1 to 10 pg total PAHs/kg fresh weight, that smoking or barbecuing fish and meats increases total PAH content up to 100-fold, that contaminated molluscs and crustaceans may contribute significantly to PAH intake, and that PAH carcinogenic risk to humans has existed at least since man began to... 

The limitations in using the TEF approach for the assessment of PAH carcinogenicity following oral administration was illustrated when it was used on the carcinogenicity data and the analytical data on the PAH composition in the coal tars used in the study by Culp et al. (1998). When the TEF values derived by Larsen and Larsen (1998) were used (Table 10.4), the carcinogenic potency of both coal-tar mixtures was predicted to be only approximately 1.5 times that of the benzo[a]pyrene content. However, the observed potencies of the coal-tar mixtures were up to 5 times that accounted for by the benzo[a]pyrene content. In this case, the use of the TEF approach for PAH carcinogenicity would underestimate it. 

Figure 14.8 Potent PAH carcinogens with a bay/fjord region.

The significance of these low levels of PAH carcinogens in food is difficult to assess. Undoubtedly, they are among the most potent carcinogens known, and every effort should be made to reduce their concentration in food. There are no clear indications, however, that they cause human cancer. .. Furthermore, there are indications that low levels of [benzo[a]pyrene], probably one of the most potent of the PAH found in food, do not produce tumors in experimental animals. The repeated application of 1.25 Xg of [benzo[a] pyrene] in acetone to the skin of mice for 68 weeks failed to produce tumors [Roe (3310, 3311)] dietary intake of 100 ppm of [benzo[a]pyrene] or less also had no effect in mice [Neal and Rigdon (2687]. 

The carcinogenicity of tar and other PAH containing materials was first demonstrated in animal experiments in the early 1900. Dibenzo[a,h]anthracene (DBA), synthesised in 1929, and benzo[a]pyrene (BaP), isolated from pitch in 1930, were the first pure PAH s shown to be carcinogenic to animals. The first review article on PAH carcinogenicity in mice was published in 1932 [40]. The Iball carcinogenicity index calculated from tumour incidence and latent period has been introduced in 1939 [4,41]. It is defined as ... 

It is of interest to investigate whether a TC intercalation between base pairs could accelerate the reaction(s) leading to covalently bonded PAHDE -DNA adducts. Surprisingly, DNA-TC complexes have become the object of molecular modelling only very recently [112]. The aim of the studies has been to find an explanation for the enantiomeric stereoselectivity and shape dependence of PAH carcinogenicity in terms of steric and energetic compatibility of the bay-region TC s with the B-DNA structure. 

In general, PAH carcinogens transform cells through genetic injury involving metabolism of the parent compound to a reactive diol... 

Benzo(a)- pyrene (PAH) Carcinogenic Mutagenic Teratogenic H Bioaccumulation H L H H... 

Nonalternant PAEIs, e.g., benzofluoranthenes, exert their genotoxic effects through their reactive metabolites. Peroxidating enzyme systems in various body tissues also can form free radicals. These free radicals produced bind to C8 and N7 in guanine and N7 of adenine in DNA. The significance of this pathway for PAHs carcinogenicity has not been evaluated. 

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