Abstract
Ethidium bromide (3, 8โdiaminoโ5โethylโ6โphenylphenanthridinium bromide) and euflavine (3, 6โdiaminoโ10โmethylacridinium chloride) are superficially similar in structure and ability to intercalate into DNA. However, they exhibit qualitative differences in their ability to bring about a mitochondrial mutation (ฯ^+^ โ ฯ^โ^) in Saccharomyces cerevisiae. This investigation tried to establish and compare the essential structural prerequisites in three series of planar, heterocyclic dyes: the phenanthridines (P series), the acridines (A series), and molecules with different heteroatoms related to acridines (X series). Compounds capable of bringing about the mutation in the complete absence of growth and energy sources are restricted to diโprimary amines in the P series: quaternization of the ring nitrogen, and an aromatic side chain at Cโ6 also appear essential. Compounds in the A series are mutagenic only with growing cells; quaternization (C~1~ through C~4~) is essential. The 10โallyl derivative is unusual; it is highly effective even in buffer supplemented only with an energy source. The results are interpreted in terms of a model that requires interaction of the mutagen with the mitochondrial inner membrane as well as with its DNA.