Meccanismi chemiopreventivi dei fenoli dell’olio d’ oliva nei confronti del danno cellulare indotto da xenobiotici ambientali
Author(s)
Fuccelli, Raffaela
Date Issued
December 13, 2012
Type
Doctoral Thesis
Abstract
The exposure to different environmental pollutants has been associated with an increased risk of cancer. This risk can be effectively reduced by chemopreventive interventions. In this thesis it was shown that a class of air pollutants, volatile organic compounds (VOCs) and in particular some of their epoxyde metabolites have a clear genotoxic property. Dose-response studies have allowed us to create a scale of genotoxicity for these compounds in which the styrene oxide (SO) is resulted at the first place. We also shown that the epoxyde-induced DNA damage is mediated, at least in part, by oxidative stress since the treatment of cells with the SO caused both an increase of intracellular peroxides and an accumulation of oxidized bases in DNA. Furthermore, it was observed that some well known antioxidants such as the N-acetyl-cysteine (NAC) and phenolic compounds derived from both olive oil and waste water were able to prevent the SO-induced DNA. The preventive effect of phenols was of particular interest because it was evident at very low doses (1 μg/ml) which may be reached in vivo in normal subjects following the Mediterranean diet. Finally, we wanted also to study in more detail the chemopreventive properties of hydroxytyrosol (the main phenolic compound found in olive oil) on the promotion/progression phases of carcinogenesis. The data obtained showed that at high doses (50-100 μM) this compound possesses a pro-oxidant activity which is deeply involved on its anti-proliferative and pro-apoptotic activities on tumor cells. The anti-proliferative effect of hydroxytyrosol was found to be related to a decrease of the phosphorylation of retinoblastoma protein (Rb).
It can be concluded that VOCs, through their epoxy metabolites, induce oxidative damage to DNA that may be prevented by olive oil phenols which are also abundantly present in the waste waters which represent a matrix with high environmental impact.
Additional information
Dottorato di ricerca in Scienze ambientali
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