The relationship between the chemical structures and mutagenic specificities of the DNA lesions formed by chemical and physical mutagens.

The mutagenic activities of radiation, alkylating agents, and aromatic amines and amides are examined from the perspective of relating the observed patterns of mutagenesis with the structures of the premutagenic DNA lesions. The general approach taken to establish such relationships has involved the construction of viral or plasmid genomes containing specific DNA adducts. The in vivo replication of such site-specifically modified genomes results in the induction of mutations, which are characterized by DNA sequencing. It is found that the mutation types that arise in these simple systems often match those occurring in tumors produced in mammals exposed intentionally or unintentionally to carcinogenic agents.