Mutations and loss of transforming activity of Bacillus subtilis DNA after reaction with esters of carcinogenic N-hydroxy aromatic amides.

Reaction of the sulfuric acid ester of /V-hydroxy-4acetylaminobiphenyl and of the acetic acid esters of /V-hydroxy-4-acetylaminobiphenyl, /V-hydroxy-4-acetylaminostilbene, and /V-hydroxy-2-acetylaminophenanthrene with transforming DNA of Bacillus subtilis in vitro caused both inactivation of transforming activity and the induction of mutations. The parent amides, amines, /V-hydroxy amides, and /V-hydroxy amines each yielded little or no inactivation or mutation of the trans forming DNA under similar conditions. These data are consistent with and in extension of our previous studies on the inactivation and mutation of transforming DNA by esters of /V-hydroxy-2-acetylaminofluorene. The magnitude of the inactivating and mutagenic ac tivity of the esters depended both on the nature of the esterified acid and of the aryl group. Sulfuric acid esters of /V-hydroxy-2-acetylaminofluorene and 7V-hydroxy-4acetylaminobiphenyl were each more active than the corresponding acetic acid esters. Under similar condi tions, the acetic acid ester of yV-hydroxy-2-acetylaminofluorene caused more inactivation and more mutations than did the acetic acid esters of the other 3 /V-hydroxy amides. In all cases, there was an approximately linear relationship between the extent of inactivation (expressed as lethal hits) and the frequency of mutations; the slopes of these lines were similar for all the esters studied. The synthesis of /V-hydroxy-2-aminophenanthrene, a new compound, is described.