Abstract
<b>Background</b>
Selenium (Se) is an essential micronutrient that may exert cancer-selective cytotoxicity at
supranutritional exposures. It has been proposed Se exerts these effects, in part, by affecting
DNA damage and repair. This project investigated the effects of Se on DNA repair enzyme
activities in cancer cell lines and peripheral blood mononuclear cell (PBMC) samples from
chronic lymphocytic leukaemia (CLL) and metastatic solid tumour (MST) patients.
<b>Methods</b>
Effects of different forms of Se on cell viability, intracellular reactive oxygen species (ROS)
and DNA repair activities were examined in T-cell leukaemic (Jurkat E6-1) and prostate cancer
(LNCaP) cell lines. DNA repair activities were measured in PBMC samples from the first
round of the dose escalation study, in which patients took 400µg/day of sodium selenite (SS),
methylselenocysteine (MeSeCys) or selenomethionine (SeMet) for 8 weeks.
<b>Results</b>
SS and methaneseleninic acid (MSA) induced cytotoxic effects in Jurkat and LNCaP cells. SS
treatment induced Jurkat cell death in a ROS-independent manner. SS (5µM) significantly
decreased Jurkat DNA ligase and polymerase β (POLβ) activities (p<0.05 and p<0.01,
respectively). MSA (1µM) and MeSeCys (10µM) significantly increased Jurkat POLβ activity
(p<0.05 and p<0.01, respectively). No significant Se-induced changes in LNCaP POLβ activity
or in DNA repair activities in patient PBMC samples.
Correlation analysis suggested coordinated expression of DNA repair enzymes in cell lines and
patient PBMCs. Substantial inter-individual variability in DNA repair activities was identified
in patient PBMCs and baseline APE-1 activity was significantly higher in the CLL than in MST
patients (p<0.01).
<b>Conclusions</b>
This research provides the first direct evidence that Se regulates DNA repair in a form-,
concentration- and cell type-specific manner. Se had no detectable effect on DNA repair
enzyme activities in cancer patients, perhaps due to insufficient dosage. CLL patients exhibited
elevated APE-1 activity suggesting circulating leukaemic cells have abnormal DNA repair
enzyme profiles.