Methylglyoxal-bis(guanylhydrazone) (
MGBG), a
polyamine analogue, has been known to inhibit the biosynthesis of
polyamines, which are important in cell proliferation. We showed that
MGBG treatment significantly affected γ-radiation-induced cell cycle transition (G(1)/G(0)→S→G(2)/M) and thus γ-radiation-induced cell death. As determined by micronuclei and comet assay, we showed that it sensitized the cytotoxic effect induced by γ-radiation. One of the reasons is that
polyamine depletion by
MGBG treatment did not effectively protect against the chemical (
OH) or physical damage to
DNA caused by γ-radiation. Through in vitro experiment, we confirmed that
DNA strand breaks induced by γ-radiation was prevented more effectively in the presence of
polyamines (
spermine and
spermidine) than in the absence of
polyamines.
MGBG also blocks the cell cycle transition caused by γ-radiation (G(2) arrest), which helps protect cells by allowing time for DNA repair before entry into mitosis or apoptosis, via the down regulation of
cyclin D1, which mediates the transition from G(1) to S phase of cell cycle, and
ataxia telangiectasia mutated, which is involved in the
DNA sensing, repair and cell cycle check point. Therefore, the abrogation of G(2) arrest sensitizes cells to the effect of γ-radiation. As a result, γ-radiation-induced cell death increased by about 2.5-3.0-fold in cells treated with
MGBG. However, exogenous
spermidine supplement partially relieved this γ-radiation-induced cytotoxicity and cell death. These findings suggest a potentially therapeutic strategy for increasing the cytotoxic efficacy of γ-radiation.