Carcinogenicity hydrocarbons

Another way in which Pt could bind to DNA is through the formation of intercalation compounds. The parallel here is with the hydrocarbon carcinogens and the nucleic acid stains, the acridines. It has been shown that metal chelates will form this same type of jt-complex. For example, palladium oxinate will form exactly the same type of -complexes as anthracene (88). 

The search for an alternative reactive metabolite for the polycyclic hydrocarbon carcinogens was soon successful. Also in 1973, Borgen et al. (54) reported that, in the presence of a microsomal system from hamster liver, trans 7,8-dihydro-7,8-dihydroxybenzola]-pyrene (a metabolite of benzo[aJpyrene) was bound to DNA in vitro some ten times more extensively than was benzo[a]pyrene itself. 

It should be emphasized, however, that this relationship for genetically determined enzyme toxicity has been worked out in detail only with polycyclic hydrocarbon carcinogens. It remains to be determined how many other classes of carcinogens may also show such differences. 

A CASE-SAR analysis of polynuclear aromatic hydrocarbon carcinogenicity. Mutat. Res., 242, 285-303. 

Animal carcinogen One of several heterocyclic analogues of the polycyclic aromatic hydrocarbon carcinogens synthesized by Buu-Hoi et al. 

P16) (32,76)] hydrocarbons carcinogens, and detoxification metabolism. Arg554Lys polymorphism... 

These analyses show major differences in the DNA reaction products formed by DMBA and by BP, a weaker but much more extensively studied polycyclic aromatic hydrocarbon carcinogen (35). 

Dibenzofuran induces hepatic, skin, and lung cytochrome P450 lAl, 1A2, and aryl hydrocarbon hydroxylase in rats. Thus, toxicity results from aryl hydrocarbon receptor signal transduction pathway. Bioactivation of many polycyclic hydrocarbon carcinogens is mediated by these enzymes. 

These results show that pattern recognition can be used as an effective tool to characterize polycyclic aromatic hydrocarbon carcinogens. Using a set of only 28 molecular structure descriptors, linear discriminants can be found to correctly dichotomize 191 out of 200 randomly selected PAH s. This same set of 28 descriptors supports a linear discriminant function that has an average predictive ability of over ninety percent when subjected to randomized predictive ability tests. 

The carcinogenicity of dimethylnitrosamine and 4-nitrosomorpholine was reduced by deuterium substitution for hydrogen on carbon atoms alpha to the amino nitrogen.81 82 Consistent with the hypothesis that alpha-carbon oxidation is required for reactive metabolite formation from nitrosamines, there is a substantial primary deuterium isotope effect (ku/kg = 3.8) on the rate of dimethylnitrosamine N-demethylation. 3 Specific deuteration of 3-methylcholanthrene, a potent polycyclic hydrocarbon carcinogen, showed that oxidation of the 1-carbon atom is critical in the tumor-initiating process in mouse skin. ... 

Stable Isotopes other than deuterium have also been used in some novel approaches for studying reactive metabolite formation. Benzo[a]pyrene, another potent polycyclic hydrocarbon carcinogen, was incubated with cofactors and rat liver mlcrosomes in an atmosphere of g Oj to investigate whether or not 6-oxybenzo[a]pyrene radical was formed. Electron spin... 

Biological activation of polycyclic-hydrocarbon carcinogens proceeds through dihydrodiols and diol epoxides and such pathways are clearly possible for aza-aromatic compounds. To assist in investigating the existence of such routes, a range of dihydrodiols and diol epoxides of benz[c]acridine and benz[a]acridine (R.E. Lehr and S. Kumar, J. org. Chem., 1981, 367 ... 

Bulay OM, Wattenberg LW. 1971. Carcinogenic effects of polycyclic hydrocarbon carcinogen administration to mice during pregnancy on the progeny. J Natl Cancer Inst 46 397-402. 

Dipple A, Bigger CAM. 1991. Mechanism of action of food-associated polycyclic aromatic hydrocarbon. Carcinogens. Mutat Res 259(3-4) 263-276. 

S.S. Epstein (1963). The photodynamic activity of polycyclic hydrocarbons carcinogens. Acta Unio Int. Cancrum, 19, 599-601. 

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