Molecular Pharmacology, Vol 6, 667-679, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Determination of the Mutagenic Activity to Bacteriophage T4 of Carcinogenic and Noncarcinogenic Compounds

¹ McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706

Forty-one carcinogens and four noncarcinogens were tested for mutagenic activity and the kinds of mutational events produced by the active compounds in bacteriophage T4. Twentyfive carcinogens, including many hydrocarbons, were presumed to have no mutagenic activity because they were not toxic to Escherichia coli BB or to T4 phage. Four carcinogenic inorganic salts and five chemical carcinogens (N-hydroxy-1-naphthylamine, N-hydroxy-2-naphthylamine, N-hydroxy-2-aminofluorene, 10-formyl-1,2-benzanthracene, and DL-ethionine) were toxic but not mutagenic to intracellular T4 phage. One compound of definite but low chemical reactivity (the glucuronide of N-hydroxy-2-acetylaminofluorene) was not mutagenic by direct treatment of T4 phage. Six chemically more reactive carcinogens (-propiolactone, propane sultone, N-acetoxy-2-acetylaminofluorene and its 7-fluoro derivative, glycidaldehyde, and nitrogen mustard) were mutagenic to T4 phage. The types of mutations induced by each compound were determined. The possible relationship between carcinogenesis and mutagenesis is discussed.

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ACKNOWLEDGMENTS We are grateful to Professors E. C. and J. A. Miller and R. K. Boutwell for generously supplying us with valuable compounds, and for helpful advice and discussion.