Mutagenicity and DNA Damage of Bisphenol A and Its Structural Analogues in HepG2 Cells

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 signifi cant DNA damage only after the 24-hour exposure, while analogues DMBPS, BP-1, and BP-2 induced a transient increase in DNA strand breaks observed only after the 4-hour exposure. BPF, BPAF, BPZ, and DMBPA did not induce DNA damage.
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.