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N-Benzoyloxy-N-methyl-4-aminoazobenzene: Its Carcinogenic Activity in the Rat and Its Reactions with Proteins and Nucleic Acids and Their Constituents in Vitro¹

McArdle Laboratory for Cancer Research, Medical Center, University of Wisconsin, Madison, Wisconsin 53706

N-Benzoyloxy-N-methyl-4-aminoazobenzene (N-benzoyloxy-MAB), a new derivative of the hepatocarcinogen N-methyl-4-aminoazobenzene (MAB), was synthesized. This toxic ester of N-hydroxy-MAB produced sarcomas at the site of repeated s.c. injections in rats; MAB was inactive under these conditions. Unlike MAB, N-benzoyloxy-MAB reacted readily in vitro at pH 7 with protein, RNA, and DNA to form macromolecularbound dye. Five nucleophilic components of these macromolecules (methionine, cysteine, tryptophan, tyrosine, and guanosine) reacted with N-benzoyloxy-MAB under similar conditions to form polar dyes; other common amino acid and nucleoside components did not react. The reactions of N-benzoyloxy-MAB with proteins, nucleic acids, and their components may be useful prototypes in studies on the proteinand nucleic acid-bound dyes formed in vivo by the aminoazo dyes. The biologic and chemical properties of N-benzoyloxy-MAB parallel those of the carcinogenic aromatic N-acyloxy amide N-acetoxy-2-acetylaminofluorene and lend further support to the concept that the carcinogenic aromatic amines and amides are activated in vivo by esterification of their N-hydroxy metabolites.

¹ This investigation was supported by Research Training Grant CRTY-5002 and by Program-Project Grant CA-07175 of the National Cancer Institute, USPHS; by a grant from The Jane Coffin Childs Memorial Fund for Medical Research; and by the Alexander and Margaret Stewart Trust Fund.

² Montreal Cancer Institute, Notre Dame Hospital, Montreal, Quebec, Canada.

³ Department of Education, Hirosaki University, Hirosaki, Aomori-ken, Japan.

Received 3/27/67. Accepted 5/ 6/67.

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