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EFFECTS OF THE ANTIMUTAGENS VANILLIN AND CINNAMALDEHYDE ON SPONTANEOUS MUTATION IN E. COLI LACL STRAINS AND ON GLOBAL GENE EXPRESSION IN SALMONELLA TA104 AND HUMAN HEPG2 CELLS
Shaughnessy, D. T. AND D M. DeMarini. EFFECTS OF THE ANTIMUTAGENS VANILLIN AND CINNAMALDEHYDE ON SPONTANEOUS MUTATION IN E. COLI LACL STRAINS AND ON GLOBAL GENE EXPRESSION IN SALMONELLA TA104 AND HUMAN HEPG2 CELLS. Presented at Environmental Mutagen Society, Anchorage, Alaska, 4/27/02--5/2/02.
Effects of the Antimutagens Vanillin and Cinnamaldehyde on Spontaneous Mutation in E. coli lacI Strains and on Global Gene Epression in Salmonella TAlO4 and Human HepG2 Cells
In previous work we have shown that vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutagens that reduced the spontaneous mutant frequency in Salmonella typhimurium strain TA104 (hisG428, rfa, uvrB, pKM101) by 50%. Analysis of mutation spectra of cells treated with nontoxic doses of VAN and CIN demonstrated that this reduction was due solely to a reduction in mutations at GC sites. Antimutagenesis experiments in hisG428 strains of Salmonella with varying DNA repair backgrounds showed that VAN and CIN require SOS repair genes to produce an antimutagenic effect against spontaneous mutagenesis. These studies have been extended to derivatives of the E. coli lacI strain NR9102. Treatment with either VAN or CIN reduced mutant frequency by approximately 50% at nontoxic doses in the parent strain NR9102 (ara, thi, L\prolac, F'prolac). In NRl1475 (ara, thi, L\prolac, recA430, F'prolac) , a strain with a mutation in the recA gene that interferes with SOS repair but allows for normal recombination, both VAN and CIN effectively reduced mutant yield with minimal cytotoxicity. However, in NRl1317 (ara, thi, lprolac, recA56, F'prolac) , which is deficient in both SOS repair and recombination, no antimutagenic effect was observed. In the JER-deficient strains, NR10241 (ara, thi, L\prolac, uvrA277, "'prolac) and NRl1634 (ara, thi, L\prolac, uvrB5, F'prolac) , only VAN produced an antimutagenic effect. To explore possible antigenotoxic effects of VAN and CIN in human HepG2 cells, we have used the Comet Assay. Preliminary results indicate that VAN treatment reduces tail moment relative to untreated cells. We have also begun to examine the effects of VAN and CIN on gene expression in HepG2 cells and in Salmonella TA104. Preliminary microarray results with HepG2 cells indicate that treatment with1OO-uM CIN induces a two-fold up-regulation of thioredoxin (TRDX) , glutathione peroxidase (GSHPX) , and glutathione S- :ransferase (GST1) . Apolipoproteins (APOA1, APOC2, and APOE) , alpha-2-HS glycoprotein, IGF-binding protein (IGFBP1) and prosaposin (PSAP) were down regulated approximately two-fold.
Abstract does not necessarily represent policy of the US EPA.]