The instability of (GpT)n and (ApC)n microsatellites induced by formaldehyde in Escherichia coli

Formaldehyde, a potential human nasal carcinogen, has been reported to induce DNA lesions. However, the effect of formaldehyde on microsatellite instability has not previously been reported. Plasmids containing different lengths of complementary (ApC)(n) or (GpT)(n) dinucleotide repeats on the leading strand were constructed to investigate whether the mutagenesis by formaldehyde can contribute to microsatellite instability. We observed that exposure of Escherichia coli to 2.5 mM formaldehyde increased the frequency of expansions and deletions of the dinucleotide repetitive sequences. After being induced by formaldehyde, the microsatellite mutation frequencies of (GpT)(n) and (ApC)(n) were 2- to 24-fold higher than those in the control. Although complementary to each other, (ApC)(n) and (GpT)(n) had different mutation frequencies when they were on the leading strand: mutation frequencies of (GpT)(n) were 13- to 24-fold higher than the control group, whereas frequencies of (ApC)(n) were only 2- to 3-fold higher the control group. Sequencing of the repetitive and flanking sequences in mutant clones showed that all mutants displayed expansions or deletions of dinucleotide repeats. These results clearly suggest that formaldehyde can increase microsatellite instability by affecting the fidelity of microsatellite maintenance. We presumed that a mutagenic mechanism of formaldehyde and the temporal formation of left-handed helix Z-DNA might be related to the microsatellite instability.