Effect of eugenol on the genotoxicity of established mutagens in the liver.
The influence of in vivo treatment with eugenol on established mutagens was studied to determine whether eugenol has antigenotoxic potential. The effects of eugenol in rats was investigated in the unscheduled DNA synthesis (UDS) assay with established mutagens and the Salmonella typhimurium mutagenicity assay. In addition, the effect of in vivo treatment with eugenol on benzo[a]pyrene (B[a]P)-induced genotoxicity in human hepatoma cell line Hep G2 was investigated in the single-cell gel electrophoresis assay. The mutagenicity of B[a]P in the S. typhimurium mutagenicity assay was lower in liver S-9 fractions from control rats. Incubation of liver S-9 fractions from eugenol-treated rats with dimethylbenzanthracene (DMBA) had no antimutagenic effect. Eugenol did not modify UDS activity in hepatocytes isolated from rats pretreated with eugenol orally after exposure of these cells in vitro to DMBA and aflatoxin B1. Four different treatment schemes of combinations of B[a]P and eugenol were examined in Hep G2 cells: pre-treatment with eugenol; simultaneous treatment with eugenol and B[a]P; a combination of these (pretreatment/simultaneous treatment); and post-treatment with eugenol. An increase in the genotoxicity of B[a]P was found in Hep G2 cells. No effect of eugenol on the genotoxicity of B[a]P was found with the pre- and post-treatments. It is concluded that the effect of eugenol on genotoxicity induced by established mutagens is not univocal; in vivo treatment of rats with eugenol resulted in a reduction of the mutagenicity of B[a]P in the S. typhimurium mutagenicity assay, while in the UDS assay no effect of eugenol was found. In vitro treatment of cultured cells with eugenol resulted in an increase in genotoxicity of B[a]P. These findings indicate that there is only limited support for the antigenotoxic potential of eugenol in vivo.
Rompelberg
C J
CJ
TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Evertz
S J
SJ
Bruijntjes-Rozier
G C
GC
van den Heuvel
P D
PD
Verhagen
H
H
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D016604:Aflatoxin B1 / Q000633:toxicity; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000633:toxicity; D006528:Carcinoma, Hepatocellular; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D004587:Electrophoresis, Agar Gel; D005054:Eugenol / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008113:Liver Neoplasms; D008297:Male; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects; D014407:Tumor Cells, Cultured
D016587:Antimutagenic Agents; D009153:Mutagens; D001564:Benzo(a)pyrene; D005054:Eugenol; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D005982:Glutathione Transferase