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Effect of beta-carotene on catechol-induced genotoxicity in vitro: Evidence of both enhanced and reduced DNA damage
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2013 (English)In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 47, no 9, 692-698 p.Article in journal (Refereed) Published
Abstract [en]

Intake of antioxidants from the diet has been recognized to have beneficial health effects, but the potential benefit of taking antioxidants such as beta-carotene as supplements is controversial. The aim of the present study was to evaluate the potential protective effects of a physiologically relevant concentration (2 mu M) of beta-carotene on the DNA damaging effects of catechol in mouse lymphoma L5178Y cells. Two different exposure protocols were used: simultaneous exposure to beta-carotene and catechol for 3 h; and exposure to catechol for 3 h after 18 h pre-treatment with the vitamin. DNA damage was evaluated using the comet assay (employing one procedure for general damage, and another procedure, which also included oxidative DNA damage). Independent of exposure protocol and procedure for comet assay, beta-carotene did not increase the basal level of DNA damage. However, at the highest concentration of catechol (1 mM), beta-carotene was found to clearly increase the level of catechol-induced DNA damage, especially in the pre-treated cells. Interestingly, an opposite effect was observed at lower concentrations of catechol, but the beta-carotene related reduction of catechol-induced genotoxicity was significant (P < 0.05) only for the procedure including oxidative damage induced by 0.5 mM catechol. Taken together our results indicate that beta-carotene can both reduce and enhance the DNA damaging effects of a genotoxic agent such as catechol. This indicates that it is the level of catechol-induced DNA damage that seems to determine whether beta-carotene should be regarded as a beneficial or detrimental agent when it comes to its use as a dietary supplement.

Place, publisher, year, edition, pages
2013. Vol. 47, no 9, 692-698 p.
Keyword [en]
antioxidant, comet assay, hOGG1, mouse lymphoma cells, pro-oxidant
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-206959DOI: 10.3109/10715762.2013.815346ISI: 000323107900004OAI: oai:DiVA.org:uu-206959DiVA: diva2:646653
Available from: 2013-09-09 Created: 2013-09-09 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Effects of Antioxidants and Pro-oxidants on Oxidative Stress and DNA Damage using the Comet Assay: Studies on Blood Cells from Type 2 Diabetes Subjects and Mouse Lymphoma Cells
Open this publication in new window or tab >>Effects of Antioxidants and Pro-oxidants on Oxidative Stress and DNA Damage using the Comet Assay: Studies on Blood Cells from Type 2 Diabetes Subjects and Mouse Lymphoma Cells
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diet and oral supplements comprise two distinct sources of antioxidants known to prevent oxidative stress. Beneficial effects from antioxidants have been seen for patients at risk for type 2 diabetes.

The aim of this thesis was to evaluate the positive effects of antioxidants against oxidative stress and DNA damage in type 2 diabetes subjects. We also used antioxidants as tools to determine the mechanisms behind genotoxicity induced by mutagenic pro-oxidative agents in mouse lymphoma cells. Several techniques were used to measure oxidative stress and DNA damage, but the main technique used was alkaline comet assay.

The results showed that the fruit and vegetable intake was inversely related to oxidative stress in type 2 diabetes subjects. However, oral supplementary intake of 20 antioxidants did not decrease oxidative stress biomarkers.

In studies on mouse lymphoma cells, using the alkaline comet assay, DNA damage was induced by catechol and o-phenylenediamine (OPD), while 4-nitro-o-phenylenediamine (4-NOPD) induced only oxidative damage, showing different mechanisms of action behind the mutagenicity of the compounds. Also, oxidative stress was induced by catechol and 4-NOPD, whereas imbalances in the nucleotide pool were seen after exposure to OPD or 4-NOPD. Addition of antioxidants together with these pro-oxidants showed that β-carotene was able to reduce DNA damage at low concentrations of catechol, but increased DNA damage at high concentration. In comparison, addition of α-tocopherol slightly decreased catechol-induced DNA damage at all concentrations of catechol. However, no effect of α-tocopherol was seen on OPD-or 4-NOPD-induced DNA damage.

In conclusion, antioxidants from fruits and vegetables, but not from oral supplements, reduced oxidative stress in type 2 diabetes patients, suggesting fruits and vegetables being a healthier source for antioxidant-intake, as compared to oral supplements. Different mechanisms of action for mutagenic pro-oxidants were shown in mouse lymphoma cells, introducing the nucleotide pool as an interesting target for oxidative stress. Reduction of catechol-induced DNA damage by β-carotene or α-tocopherol was shown, with a pro-oxidative action of β-carotene at high concentration of catechol, Interestingly, α-tocopherol was not able to decrease OPD- or 4-NOPD-induced DNA damage, supporting different mechanisms of action behind the genotoxicity from the three pro-oxidants.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 78 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 185
Keyword
metabolic syndrome, fruit and vegetable intake, plasma antioxidants, beta-carotene, alpha-tocopherol, inflammation, oxidative DNA damage, lipid peroxidation, mouse lymphoma assay, ROS, nucleotide pool, viability, DNA dye
National Category
Pharmacology and Toxicology
Research subject
Toxicology
Identifiers
urn:nbn:se:uu:diva-217886 (URN)978-91-554-8877-2 (ISBN)
Public defence
2014-03-28, A1:107a, Biomedical center, Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2014-03-06 Created: 2014-02-05 Last updated: 2014-04-29

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Åsgård, RikardHellman, Björn

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