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ANTIMUTAGENIC EFFECT OF CINNEMALDEHYDE DUE TO INHIBITION OF MUTATIONS AT GC SITES BUT NOT AT SITES IN SALMONELLA TA104
Citation:
Shaughnessy, D. T., R W. Setzer, AND D M. DeMarini. ANTIMUTAGENIC EFFECT OF CINNEMALDEHYDE DUE TO INHIBITION OF MUTATIONS AT GC SITES BUT NOT AT SITES IN SALMONELLA TA104. Presented at EMS Meeting, New Orleans LA, April 2000.
Description:
Vanillin and cinnemaldehyde are dietary antimutagens that reduce the spontaneous mutant frequency in Salmonella strain TA104 (hisG428, rfa, duvrB, pKM101) by 50%. To date, no study has ever demonstrated whether the antimutagenic effect of an agent is due to a reduction in all classes of mutations or to a reduction in selective classes of mutations. To explore this issue, we have determined the spontaneous mutation spectrum in TA104 as well as the mutation spectrum after a 50% reduction in mutant frequency due to treatment with vanillin or cinnemaldehyde. The spectra of the spontaneous and vanillin-treated mutants were not significantly different (p = 0.7). Vanillin, therefore, reduced all classes of mutations equally. In contrast, the spectra of the spontaneous and cinnemaldehyde treated mutants were different (p < 0.02). In this case, cinnemaldehyde reduced mutations at GC sites, but did not affect the frequency of mutations at AT sites. The entire 50% reduction in mutant frequency by cinnemaldehyde could be attributed to the reduction of mutations at GC sites alone. Both antimutagens also caused a 50% reduction in spontaneous mutant frequency in a uvrB+ strain, suggesting that nucleotide excision repair does not play a role in the antimutagenic effects of these two agents. Preliminary studies suggest that the antimutagenic effect is SOS-dependent This initial study using mutation spectra as a probe for the molecular mechanisms of antimutagens has permitted the classification of antimutagens into two general classes: those that reduce all classes of mutations equally versus those that reduce only specific classes of mutations.