Some mammalian carcinogens and their metabolites affect the viability of Salmonella typhimurium strains, as indicated by a decrease in colony formation, and also induce prophage. We determined the minimum concentration required for prophage induction and the maximum prophage induction frequency for each carcinogen. The latter value was determined by the ratio of the number of induced phage particles relative to that of spontaneously induced phage particles in the controls. This value is constant for each carcinogen, regardless of its concentration. Since damage of the bacterial genome results in prophage induction, the reactivity of each compound with the genome may be indicated by the minimum concentration required for prophage induction and the maximum frequency of prophage induction. Carcinogens unable to affect bacterial viability are also unable to induce prophage. Failure to induce prophage indicates a requirement for metabolic activation by mammalian enzymes. Interaction of these carcinogens with free phage particles in vitro was used as an index of direct interaction of carcinogen with DNA. Among 16 compounds tested, six had a direct effect on the phage genome, resulting in loss of phage viability. Five of these six compounds are hydroxylated compounds, and the other is N-acetoxy-2-acetylaminofluorene. From these observations it may be concluded that these six compounds are reactive with genomes without further metabolism.
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