Inhibition of spontaneous mutagenesis by vanillin and cinnamaldehyde in Escherichia coli: Dependence on recombinational repair

Abstract

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, ΔuvrB, 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 damageresulting in an antimutagenic effect on spontaneous mutation.

Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair

“…In addition, VAN, but not CIN, was actually mutagenic in a mismatch repair (MMR)-defective strain of E. coli [19]. Thus, we proposed that VAN and CIN produced DNA damage that elicited recombinational repair, but not other types of repair, resulting in a reduction of spontaneous mutation in bacteria [19].…”

“…Vanillin (VAN) and cinnamaldehyde (CIN) are food flavorings that inhibit induced mutations in bacteria [7][8][9][10] and mammalian cells [11][12][13][14]. Although VAN and CIN inhibit spontaneous mutation in bacteria [15][16][17][18][19], this effect has not yet been reported in mammalian cells. VAN and CIN have been classified as bioantimutagens because they can modulate cellular processes such as DNA replication and repair [18].…”

“…Recently, we demonstrated that VAN and CIN required RecA recombinational repair, but not mismatch, SOS, or nucleotide excision repair, in order to reduce spontaneous mutation in Escherichia coli [19]. In addition, VAN, but not CIN, was actually mutagenic in a mismatch repair (MMR)-defective strain of E. coli [19].…”

“…Recently, we demonstrated that VAN and CIN required RecA recombinational repair, but not mismatch, SOS, or nucleotide excision repair, in order to reduce spontaneous mutation in Escherichia coli [19]. In addition, VAN, but not CIN, was actually mutagenic in a mismatch repair (MMR)-defective strain of E. coli [19]. Thus, we proposed that VAN and CIN produced DNA damage that elicited recombinational repair, but not other types of repair, resulting in a reduction of spontaneous mutation in bacteria [19].…”

“…Because VAN was mutagenic in mismatch repair-deficient E. coli [19] and both VAN and CIN required recombinational repair in order to be antimutagenic, we evaluated the reduction of the spontaneous MF at the HPRT locus in HCT116 cells as well as the induction of DNA damage (comet assay) by VAN and CIN in both HCT116 and HCT116 + chr3 cells. In addition, we examined the influence of VAN and CIN on global gene expression in these cells in order to identify genes and pathways that might play a role in the antimutagenic effects of these agents.…”