The interaction of the 7,8-dihydrodiol-9, 10-oxides of benzo(a) pyrene with bacteriophages R17 and T7

Dose-survival curves for bacteriophages R17 and T7 treated with the syn- and anti-isomers for 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in 0.02 M phosphate buffer, pH 7.0, have been determined. In both cases the anti-isomer proved to be the more toxic: mean lethal dose for R17; syn- 3 μg/ml, anti- 2 μg/ml: and for T7, syn- 3 μg/ml, anti- 0.3 μg/ml. With both reagents reaction with bacteriophage or loss by solvolysis were complete within minutes. Physico-chemical studies of the RNA failed to detect any degradation 1 and 24 h after the addition of the reagents to the bacteriophage and no change in survival of the bacteriophage occurred during this period. In experiments with bacteriophage T7 and T7-DNA reaction did not, in the first hour, introduce any significant number of alkali-labile sites in the nucleic acid. These results suggest that no reaction occurs with the phosphate groups of the nucleic acids. Following the initial loss of infectivity when bacteriophage T7 was treated with the syn-isomer there was a further, progressive loss of biological activity over 4 days which was associated with the development of alkali labile lesions. It seems probable that these latter effects are due to the loss of alkylated bases from the DNA, a process similar to the depurination reactions observed following the reaction of DNA with e.g. methylating agents.