Shaughnessy Daniel T, Schaaper Roel M, Umbach David M, DeMarini David M
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, NC 27709, USA.
Mutat Res. 2006 Dec 1;602(1-2):54-64. doi: 10.1016/j.mrfmmm.2006.08.006. Epub 2006 Sep 26.
Vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutagens that effectively inhibit both induced and spontaneous mutations. We have shown previously that VAN and CIN reduced the spontaneous mutant frequency in Salmonella TA104 (hisG428, rfa, DeltauvrB, pKM101) by approximately 50% and that both compounds significantly reduced mutations at GC sites but not at AT sites. Previous studies have suggested that VAN and CIN may reduce mutations in bacterial model systems by modulating DNA repair pathways, particularly by enhancing recombinational repair. To further explore the basis for inhibition of spontaneous mutation by VAN and CIN, we have determined the effects of these compounds on survival and mutant frequency in five Escherichia coli strains derived from the wild-type strain NR9102 with different DNA repair backgrounds. At nontoxic doses, both VAN and CIN significantly reduced mutant frequency in the wild-type strain NR9102, in the nucleotide excision repair-deficient strain NR11634 (uvrB), and in the recombination-proficient but SOS-deficient strain NR11475 (recA430). In contrast, in the recombination-deficient and SOS-deficient strain NR11317 (recA56), both VAN and CIN not only failed to inhibit the spontaneous mutant frequency but actually increased the mutant frequency. In the mismatch repair-defective strain NR9319 (mutL), only CIN was antimutagenic. Our results show that the antimutagenicity of VAN and CIN against spontaneous mutation required the RecA recombination function but was independent of the SOS and nucleotide excision repair pathways. Thus, we propose the counterintuitive notion that these antimutagens actually produce a type of DNA damage that elicits recombinational repair (but not mismatch, SOS, or nucleotide excision repair), which then repairs not only the damage induced by VAN and CIN but also other DNA damage-resulting in an antimutagenic effect on spontaneous mutation.
香草醛（VAN）和肉桂醛（CIN）是膳食抗诱变剂，可有效抑制诱导突变和自发突变。我们之前已经表明，VAN和CIN可使鼠伤寒沙门氏菌TA104（hisG428、rfa、ΔuvrB、pKM101）中的自发突变频率降低约50%，并且这两种化合物均能显著降低GC位点的突变，但对AT位点的突变没有影响。先前的研究表明，VAN和CIN可能通过调节DNA修复途径，特别是通过增强重组修复来减少细菌模型系统中的突变。为了进一步探究VAN和CIN抑制自发突变的基础，我们确定了这些化合物对来自具有不同DNA修复背景的野生型菌株NR9102的五种大肠杆菌菌株的存活率和突变频率的影响。在无毒剂量下，VAN和CIN均显著降低了野生型菌株NR9102、核苷酸切除修复缺陷型菌株NR11634（uvrB）以及重组功能正常但SOS缺陷型菌株NR11475（recA430）中的突变频率。相比之下，在重组缺陷和SOS缺陷型菌株NR11317（recA56）中，VAN和CIN不仅未能抑制自发突变频率，实际上还增加了突变频率。在错配修复缺陷型菌株NR9319（mutL）中，只有CIN具有抗诱变作用。我们的结果表明，VAN和CIN对自发突变的抗诱变作用需要RecA重组功能，但与SOS和核苷酸切除修复途径无关。因此，我们提出了一个与直觉相反的观点，即这些抗诱变剂实际上会产生一种DNA损伤，引发重组修复（而非错配、SOS或核苷酸切除修复），这种修复不仅能修复VAN和CIN诱导的损伤，还能修复其他DNA损伤，从而对自发突变产生抗诱变作用。
