Molecular Geometry and Carcinogenic Activity of Aromatic Compounds. New Perspectives

Abstract

Publisher Summary This chapter focuses on the molecular geometry and carcinogenic activity of aromatic compounds. An increasing body of evidence indicates that a variety of carcinogens bind covalently to both proteins and nucleic acids, and the results of two reports suggest an approximate parallelism between carcinogenic activity and binding in the target tissue to proteins and to DNA. It has been demonstrated contrary to earlier data that 9,10-dimethyl-1,2,5,6-dibenzanthracene is a strong carcinogen. Dimethyl substitution of 1,2-benzanthracene-type molecules in the 9,l0-positions enhances carcinogenicity. Substitution in the mesoanthracenic positions considerably increases carcinogenicity in the 1,2-benzanthracene series. In the dibenzopyrene series, however, substitutions in equivalent positions produce an opposite effect. For very large-size polycyclic carcinogens, such as the tribenzopyrenes and tricycloquinazolines, interaction with critical cellular receptor site(s) may involve only part of the polycyclic molecule. There is a vast body of evidence showing that carcinogenic polycyclic aromatic hydrocarbons are formed in the pyrogenation of almost any kind of organic material. High temperatures produce the cracking of carbon compounds and repolymerization of the resulting molecular fragments, and also bring about the loss of hydrogen, leading to the aroniatixation of the polycyclic carbon skeletons formed. Because every polycyclic hydrocarbon is the structural analog of a large number of heteroaromatic isomers, it is likely that a great variety of carcinogenic compounds will be found among the heteroaromatic compounds. The finding that the presence of a naphthacene grouping in a hydrocarbon molecule is unfavorable for a high level of carcinogenic activity is also valid in the acridine series. The intercalation of hydrocarbons and other polycyclic carcinogens bring about alteration of the base sequence. The polarization bonding between the alternately stacked hydrocarbon molecules and bases promotes plane-parallel molecular adlineation and keto→enol-type, lactam–lactim tautomerism. Carcinogenic hydrocarbons also may give rise to reactive radical species in the tissues.