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.
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Authors | Stoimir Kolarević, Dragana Milovanović, Margareta Kračun-Kolarević, Jovana Kostić, Karolina Sunjog, Rajko Martinović, Jelena Đorđević, Irena Novaković, Dušan Sladić, Branka Vuković-Gačić |
Journal | Drug and chemical toxicology
(Drug Chem Toxicol)
Vol. 42
Issue 2
Pg. 130-139
(Mar 2019)
ISSN: 1525-6014 [Electronic] United States |
PMID | 29299944
(Publication Type: Journal Article)
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Chemical References |
- 3-(methylamino)avarone
- 4'-(methylamino)avarone
- Cyclohexenes
- Mutagens
- Sesquiterpenes
- avarone
- avarol
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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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