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Reducing sugars such as glucose or glucose 6-phosphate (Glc-6-P) have been shown previously to modify the amino groups of nucleotides and single-stranded DNA. We have examined the mutagenic effect of Glc-6-P-induced lesions in the double-stranded DNA plasmid pBR322. Seventeen mutants of the Ampr Tets phenotype were isolated from plasmid preparations whose transforming capacity had been decreased by incubation with Glc-6-P. A number of the mutant plasmids were found to have undergone gross DNA alterations, including insertions and deletions, as well as the development of multiple species originating from a single cell. The ability of an endogenous reducing sugar to induce extensive DNA rearrangements suggests that these lesions may be significant contributors to cellular mutation.
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