Apoptosis and changes in glucose transport early after treatment of Morrishepatoma with gemcitabine

Apoptosis has been described as an energy consuming process. This combined in vivo/in vitro study investigated the effects of the antineoplastic agent gemcitabine on tumour metabolism and on the induction of apoptosis. Dynami c positron emission tomography (PET) measurements of fluorine-18 fluorodeox yglucose (FDG) uptake were done in rats bearing Morris hepatoma prior to an d after therapy with 90 mg gemcitabine/kg b.w. Furthermore, thymidine (TdR) incorporation into the DNA of these tumours was determined. In vitro measu rements of FDG and TdR uptake were performed immediately and 24 h after the end of gemcitabine treatment, and the amount of apoptotic cells was determ ined using the TUNEL reaction. In vivo an increase in FDG transport and pho sphorylation occurred early after gemcitabine treatment, although TdR incor poration into the DNA of the tumours declined. In vitro, an enhanced glucos e transport, an increase in TdR uptake in the cytoplasm and a decrease in T dR incorporation in the nucleic acid fraction early after treatment occurre d. Inhibition of glucose transport caused an increase in the amount of apop totic cells. The increase in glucose uptake and TdR metabolism early after therapy is interpreted as a stress reaction of the tumour cells, protecting the cells from apoptosis during this early period after exposure to cytoto xic drugs like gemcitabine.