This paper is an attempt to initiate a discussion about the causes of radiation-induced mutagenesis. It considers the evidence for the involvement of singly base-damaged sites as sources of this mutagenesis. Several sets of published data are examined: These include endogenous levels of oxidized bases and their production by natural oxidative processes, and yields of mutants produced by hydrogen peroxide and by high-LET radiation. These considerations lead to the conclusion that, at the levels at which they are produced by ionizing radiation, DNA base-damaged sites are not a cause of radiation-induced mutagenesis. In analogy with previous work we invoke the involvement of multiply damaged sites (such as double-strand breaks) produced by radiation as the causative lesions.

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