Metabolism of N-Containing Polycyclic Aromatic Hydrocarbons

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This research aimed at establishment of the metabolic process involved in the activation of genotoxic N-containing polycylic aromatic hydrocarbons. The bay-region theory was proposed by Jerina, one of the counterparts of this joint research, on the activation of polycyclic aromatic hydrocarbons, but no systematic study hasnot yet been achieved on the activation of those containing hetero atom(s) such nitrogen and oxygen in the aromatic system. We have revealed that the activated form of quinoline may be the 2, 3-oxide of quinoline 1, 4-hydrate, which is a new type of activated epoxide different from the bay-region epoxides proposed to polycyclic aromatic hydrocarbons. This working hypothesis has been further evidenced by the matabolism of halogno- and methyl-substituted quinoline derivatives. Based on this activation methanism, we proposed that, when fluorine is substituted on the position-3 of the quinoline ring, those derivatives would be completely deprived of genotoxicity. This proposal has been experimentally proven with several examples.In the latter part of this 3-year joint research, we have extended the study to the bioactive lignin-related compounds, which are the oxygen-containing polymeric aromatic compounds. We found that several natural and synthetic lignins had diverse biological activities including antiviral and antimicrobial activity, and in addition, immunopotenting activity. Lignin skeletal structure is essentially required for the antiviral activity, whereas some hemicellulose appendages attached to the lignin skeleton are also required for immunopotentiating activity leading to antimicrobial activity. This research strongly suggests that more attention should be paid to the lignified materials, both natural and synthetic, as a potential medicinal resource.