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Evaluation of genotoxic potential of avarol, avarone, and its methoxy and methylamino derivatives in prokaryotic and eukaryotic test models.

Abstract
In this study, mutagenic and genotoxic potential of anti-tumor compounds avarol, avarone, and its derivatives 3'-methoxyavarone, 4'-(methylamino)avarone and 3'-(methylamino)avarone was evaluated and compared to cytostatics commonly used in chemotherapy (5-fluorouracil, etoposid, and cisplatin). Mutagenic potential of selected hydroquinone and quinones was assessed in prokaryotic model by the SOS/umuC assay in Salmonella typhimurium TA1535/pSK1002. Genotoxic potential was also assessed in eukaryotic models using comet assay in human fetal lung cell line (MRC-5), human adenocarcinoma epithelial cell line (A549), and in human peripheral blood cells (HPBC). The results indicated that avarol and avarone do not exert mutagenic/genotoxic potential. Among the studied avarone derivatives, mutagenic potential was detected by SOS/umuC test for 3'-(methylamino)avarone, but only after metabolic activation. The results of comet assay indicated that 3'-methoxyavarone and 3'-(methylamino)avarone have a significant impact on the level of DNA damage in the MRC-5 cell line. Genotoxic potential was not observed in A549 cells or HPBC probably due to a different uptake rate for the compounds and lower in metabolism rate within these cells.
AuthorsStoimir Kolarević, Dragana Milovanović, Margareta Kračun-Kolarević, Jovana Kostić, Karolina Sunjog, Rajko Martinović, Jelena Đorđević, Irena Novaković, Dušan Sladić, Branka Vuković-Gačić
JournalDrug and chemical toxicology (Drug Chem Toxicol) Vol. 42 Issue 2 Pg. 130-139 (Mar 2019) ISSN: 1525-6014 [Electronic] United States
PMID29299944 (Publication Type: Journal Article)
Chemical References
  • 3-(methylamino)avarone
  • 4'-(methylamino)avarone
  • Cyclohexenes
  • Mutagens
  • Sesquiterpenes
  • avarone
  • avarol
Topics
  • A549 Cells
  • Cell Line, Tumor
  • Comet Assay
  • Cyclohexenes (toxicity)
  • DNA Damage
  • Humans
  • Male
  • Mutagens (toxicity)
  • Salmonella typhimurium (drug effects)
  • Sesquiterpenes (toxicity)
  • Toxicity Tests

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