Chemical Carcinogenesis by Polycyclic Aromatic Hydrocarbons

Abstract

The realization that for a vast number of toxic effects, not the given compound itself was responsible but rather a metabolite that was produced from the compound, brought about an enormous step forward in chemical carcinogenesis and in toxicology in general (1–15). In chemical mutagenesis and in chemical carcinogenesis very often coumpounds, which by themselves are chemically inert, will produce mutagenic and carcinogenic effects. A prime example of this is the polycyclic aromatic hydrocarbons, which consisting of condensed aromatic rings are chemically inert, yet do produce mutagenic and carcinogenic effects. During the last 10 to 20 years researchers have started to realize that this is because they are metabolized to electrophilic metabolites which chemically react and combine with nucleophilic sites in the tissue (1–15). These nucleophilic sites include nitrogen atoms, sulphur atoms, and oxygen atoms in nucleic acids, in proteins and in carbohydrates, e.g. in carbohydrates which are parts of cellular membranes. This brings about two levels of control, the first determined by the chemical properties of the reactive metabolite, the second determined by the enzymic control of its concentration.