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Mutagenicity and DNA Damage of Bisphenol a and its Structural Analogues in Hepg2 Cells

Anja Fic1 / Bojana Žegura2 / Marija Sollner Dolenc1 / Metka Filipič2 / 3

1Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia

2National Institute of Biology, Department for Genetic Toxicology and Cancer Biology, Ljubljana, Slovenia

3Faculty of Pharmacy, University of Ljubljana Aškerčeva 7, 1000 Ljubljana, Slovenia

This content is open access.

Citation Information: Archives of Industrial Hygiene and Toxicology. Volume 64, Issue 2, Pages 189–200, ISSN (Print) 0004-1254, DOI: 10.2478/10004-1254-64-2013-2319, July 2013

Publication History

Published Online:
2013-07-02

Environmental oestrogen bisphenol A (BPA) and its analogues are widespread in our living environment. Because their production and use are increasing, exposure of humans to bisphenols is becoming a significant issue. We evaluated the mutagenic and genotoxic potential of eight BPA structural analogues (BPF, BPAF, BPZ, BPS, DMBPA, DMBPS, BP-1, and BP-2) using the Ames and comet assay, respectively. None of the tested bisphenols showed a mutagenic effect in Salmonella typhimurium strains TA98 and TA100 in either the presence or absence of external S9-mediated metabolic activation (Aroclor 1254-induced male rat liver). Potential genotoxicity of bisphenols was determined in the human hepatoma cell line (HepG2) at non-cytotoxic concentrations (0.1 μmol L-1 to 10 μmol L-1) after 4-hour and 24-hour exposure. In the comet assay, BPA and its analogue BPS induced significant DNA damage only after the 24-hour exposure, while analogues DMBPS, BP-1, and BP-2 induced a transient increase in DNA strand breaks

Sažetak

Okoljski estrogen, bisfenol A (BPA), in njegovi strukturni analogi so v veliki meri prisotni v našem okolju. Ker njihova proizvodnja in uporaba naraščata, je vse pomembneje ovrednotiti njihovo toksičnost zaradi izpostavljenosti ljudem. Z Amesovim in kometnim testom smo ovrednotili mutagenost in genotoksičnost osmih strukturnih analogov BPA (BPF, BPAF, BPZ, BPS, DMBPA, DMBPS, BP-1 in BP-2). Nobeden od testiranih bisfenolov ni izkazoval mutagenega delovanja na sevih TA98 in TA100 Salmonelle tryhimurium v prisotnosti in odsotnosti metabolne aktivacije (z Aroklorom 1254 inducirani encimi podganjih jeter). Potencialno genotoksičnost pa smo določali s kometnim testom na celični liniji humanega hepatoma (HepG2) pri necitotoksičnih koncentracijah (0.1 μmol L-1 do 10 μmol L-1) po 4-urni in 24-urni izpostavljenosti. BPA in njegov analog BPS sta pri kometnem testu povzročila poškodbe DNA samo po 24-urni izpostavljenosti, medtem ko so analogi DMBPS, BP-1 in BP-2 povzročili prehodne poškodbe DNA (samo po 4-urni izpostavljenosti). BPF, BPAF, BPZ in DMBPA niso povzročili poškodb DNA.

Keywords : Ames test; bisphenols; comet assay; genotoxicity

Ključne Besede : Amesov test; bisfenoli; kometni test

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