Glucose starvation impairs NER and γ-H2AX after UVB irradiation

Glucose is the major source for energy production. As tumor cells have higher glucose requirement, combination of glucose restriction and radio- and chemo-therapy has been explored. In this study, impairment of UVB-induced DNA damage repair response (DDR) by glucose starvation was revealed. Human keratinocytes and skin carcinoma cells were cultured in medium containing 0, 2.5, 5.5 and 25 mM glucose. Glucose restriction suppressed cell proliferation and histone acetylation. UVB exposure formed similar levels of pyrimidine dimers in all glucose conditions, whereas the repair tended to be delayed in low glucose medium. The repair molecules, TFIIH and XPG, were accumulated to DNA damaged sites regardless of glucose supply levels, but the release was delayed in glucose-starved cells. The remaining pyrimidine dimers would induce the collapse of replication forks during S phase, resulting in phosphorylation of histone H2AX (γ-H2AX), but the γ-H2AX in cells cultured in glucose-deleted medium was unexpectedly decreased. This might be due to the suppression of DNA replication by glucose deletion. This was further confirmed by the decrease in the formation of DNA double strand breaks in glucose-starved cells. These results suggested that condition of energy supply might affect UV-induced DDR.