Jcc. Ribeiro et al., Caffeine-increased radiosensitivity is not dependent on a loss of G2/M arrest or apoptosis in bladder cancer cell lines, INT J RAD B, 75(4), 1999, pp. 481-492
Purpose: Bladder cancer cell lines UCRU-BL-13, UCRU-BL-17/2 and UCRU-BL-28,
with differing p53 status and molecular responses to irradiation, were use
d to investigate possible mechanisms for caffeine-induced radiosensitizatio
n.
Materials and methods: After treatment with caffeine and exposure to X-radi
ation, radiosensitivity was determined by clonogenic assay. Cell-cycle arre
st and apoptosis were measured by flow cytometry.
Results: Both BL-13 and BL-28 cells (each expressing p53 with a wild-type s
equence) fail to arrest at the G2 checkpoint after radiation, but neverthel
ess caffeine did induce radiosensitization. In contrast, in BL-17/2 cells (
expressing p53 with a point mutation in codon 280), caffeine treatment abro
gated the radiation-induced G2 arrest but was not accompanied by radiosensi
tization. No effects on radiosensitivity were seen in RT112 cells (expressi
ng a functionally defective p53) at low caffeine doses (2mM), but at higher
doses (4mM and 10mM) caffeine caused both abrogation of radiation-induced
G2 arrest and radiosensitization. In none of the cell lines examined did ca
ffeine treatment and/or irradiation result in apoptosis.
Conclusions: In contrast with previous studies, the data suggest that radio
sensitization induced by caffeine is not dependent on abrogation of G2 arre
st or the induction of apoptosis, and is not selective for cells expressing
p53 proteins with mutations.