The mutagenic potential of vitamin C on human lymphocytes and native nucleic acids
THEODORE S. LIALIARIS1*, ANASTASIA A. PANTAZAKI3, FOTINI E. PAPACHRISTOU1, EMMANOUIL LYRATZOPOULOS1, KONSTANTINOS NATSIS1 and ALEXANDER H. KORTSARIS2

1 Laboratory of Genetics, Medical School, Democritus University of Thrace, Alexandroupolis 681 00, Greece
2 Laboratory of Biochemistry, Medical School, Democritus University of Thrace, Alexandroupolis 681 00, Greece
3 Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 541 24, Greece


Abstract

TThis study is focused on the mutagenic potential of vitamin C (Vit C, L-ascorbic acid) in various concentrations, either alone or in combination with cis-platinum (cis-Pt) in cultured human lymphocytes, using the Sister Chromatid Exchange (SCE) methodology. Human lymphocytes pretreated with high doses of Vit C, when exposed to cis-platinum, demonstrated elevated SCEs and increased cytotoxicity and cytostaticity. The effects of Vit C on certain native forms of nucleic acids were also studied, since reports have indicated that it can cause multiple breaks in plasmid DNA and lesions in nucleic acids. Therefore, the degradative ability of Vit C in supercoiled plasmid DNA, native double- and denatured single-stranded DNA was investigated (dsDNA and ssDNA, respectively). Particular Vit C concentrations also revealed cytogenetic and cytotoxic effects, and caused DNA damage in cultured human lymphocytes. High doses of Vit C (10 and 25 mM) exhibited an ability to degrade ssDNA and dsDNA. On the other hand, a low dose of Vit C (0.2 mM) demonstrated a protective effect against cis-Pt+C, as far as the cytogenetic effects are concerned. Furthermore, doses ranging from 2 to 5 mM were capable to cause non-strictly site-specific cleavage on native nucleic acids. Our findings indicate that the mutagenic potential of Vit C directly or indirectly on DNA is dependent on the concentration used and this is of importance for clinical treatment.





 
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