Inhibition of repair of X-ray-induced DNA double-strand breaks in human lymphocytes exposed to sodium butyrate.
OBJECTIVE
Sodium butyrate is known to inhibit histone deacetylase enzymes and to enhance the frequencies of X-ray-induced dicentrics and rings in human lymphocytes. In this study an investigation was made of the mechanisms underlying this enhancement by assessing the effect of sodium butyrate on the extent of X-ray-induced DNA damage and its repair in human peripheral blood lymphocytes.


METHODS
Unstimulated G0 lymphocytes were pretreated for 24h with sodium butyrate at a final concentration of 5 mM, irradiated with different doses of X-rays and then analysed for different endpoints either immediately or after different repair periods. The frequencies of DNA strand breaks were determined biochemically using nucleoid sedimentation, alkaline elution and immunochemical analysis as well as cytogenetically using the premature chromosome condensation (PCC) technique.


RESULTS
The results show that sodium butyrate pretreatment does not lead to a significant increase of DNA double- or single-strand breaks nor to an increase of alkali labile base damage in G0 lymphocytes. Moreover, sodium butyrate treatment had no effect on the initial frequency of chromosome breaks. However, PCC analysis clearly showed that the presence of sodium butyrate post-irradiation severely inhibited DNA double-strand break (DSB) repair, which most likely accounts for the increase in X-ray-induced chromosome aberrations.


CONCLUSIONS
Sodium butyrate treatment leading to changes in histone acetylation and increased accessibility of chromatin had no effect on the initial levels of X-ray-induced DNA damage. However, sodium butyrate may affect either the chromatin configuration or the enzymatic activities that play a key role in the repair of DSB.
Stoilov
L
L
Department of Radiation Genetics and Chemical Mutagenesis-MGC, Leiden University Medical Center, The Netherlands.
Darroudi
F
F
Meschini
R
R
van der Schans
G
G
Mullenders
L H
LH
Natarajan
A T
AT
D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D016192:Resting Phase, Cell Cycle
D020148:Butyric Acid