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Let me begin with an apology. My original intention was to present a synthesis of what is known about mutation and repair in the yeast and try to define a conclusive theory or single hypothesis consistent with the available data. When, however, I was confronted with the task of writing down on paper such coherent ideas, I realized my complete inadequacy to formulate any general theory. Consequently, I shall just tell you now my little story, containing some of the many possible approaches to the problem under discussion, in the hope that the theory, or the organic vision that is needed today by everybody, will result from the critical inspection and discussion of all available data, which is exactly the aim of meetings like the one we are attending.

Previously the ability of mouse erythrocytes (ER) to activate the premutagen cyclophosphamide into reactive intermediates in the yeast test with D7 strain of S. cerevisiae has been demonstrated (Teratogen Carcin Mut, 5, 223–230,1985). In a further study 2-aminofluorene (AF) showed positive mutagenicity in S. typhimurium TA 98 strain (frame-shift substitution) with mouse ER as a bioactivation system. The experiments were carried out with 1, 2 or 4 μg of AF in presence of 125 or 250 × 106 purified ER. For comparison, tests with the hepatic S9 fraction from both Aroclor 1254 or phenobarbital and β-naphthoflavone induced mice, were performed. AF is clearly mutagenic in Salmonella after previous bioactivation by ER. The genetic response is related to the amount of ER/plate. However, although it is known that the capability of ER to produce metabolically active intermediates is very low, slight differences are observed when the genotoxic effects are compared with those obtained in the presence of S9 fraction. The activating principle seems to be the partially activated oxygen in the oxyhemoglobin molecule. These results further support the hypothesis of the bioactivating ability of ER and point out the possible role of ER as producers of reactive intermediates in the blood circulation. Supported by MPI and CNR grants.