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Mutations and Loss of Transforming Activity of Bacillus subtilis DNA after Reaction with Esters of Carcinogenic N-Hydroxy Aromatic Amides¹

Radiobiology Laboratories, Yale University School of Medicine, New Haven, Connecticut 06510 [S. V. M. R., W. C. S.], and McArdle Laboratory for Cancer Research, University of Wisconsin Medical Center, Madison, Wisconsin 53706 [J. A. M., E. C. M.]

Reaction of the sulfuric acid ester of N-hydroxy-4-acetylaminobiphenyl and of the acetic acid esters of N-hydroxy-4-acetylaminobiphenyl, N-hydroxy-4-acetylaminostilbene, and N-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, N-hydroxy amides, and N-hydroxy amines each yielded little or no inactivation or mutation of the transforming 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 N-hydroxy-2-acetylaminofluorene.

The magnitude of the inactivating and mutagenic activity of the esters depended both on the nature of the esterified acid and of the aryl group. Sulfuric acid esters of N-hydroxy-2-acetylaminofluorene and N-hydroxy-4-acetylaminobiphenyl were each more active than the corresponding acetic acid esters. Under similar conditions, the acetic acid ester of N-hydroxy-2-acetylaminofluorene caused more inactivation and more mutations than did the acetic acid esters of the other 3 N-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 N-hydroxy-2-aminophenanthrene, a new compound, is described.

¹ Supported at Yale University by Program-Project Grant CA 06519 and at the University of Wisconsin by Program-Project Grant CA-07175 of the National Cancer Institute, USPHS, and at the University of Wisconsin by a grant from The Jane Coffin Childs Memorial Fund for Medical Research.

² Present address: Marygrove College, Detroit, Mich. 48221.

³ To whom requests for reprints should be sent, at the McArdle Laboratory for Cancer Research, University of Wisconsin Medical Center, Madison, Wis. 53706.

Received 11/11/69. Accepted 1/22/70.