We have examined in vitro and in vivo radioprotective effects of a well-kno
wn thiol-containing compound, dithiothreitol (DTT). The treatment of both 0
.5 and 1 mM of DTT significantly increased clonogenic survival of gamma-ray
irradiated Chinese hamster (V79-4) cells. In order to investigate the poss
ible radioprotective mechanism of DTT, we measured gamma-ray induced chromo
some aberration by micronucleus assay. In the presence of 0.5 mM or 1 mM DT
T, the frequencies of micronuclei were greatly reduced in all dose range ex
amined (1.5-8 Gy). Slightly higher reduction in micronucleus formation was
observed in 1 mM DTT-treated cells than in 0.5 mM DTT-treated cells. in add
ition, incubation with both 0.5 and 1 mM of DTT prior to gamma-ray irradiat
ion reduced nucleosomal DNA fragmentation at about same extent, this result
suggests that treatment of DTT at concentrations of 0.5 and 1 mM reduced r
adiation-induced apoptosis. In vivo experiments, we also observed that DTT
treatment reduced the incidence of apoptotic cells in mouse small intestine
crypts. in irradiated control group 4.4+/-0.5 apoptotic cells per crypt we
re observed. In DTT-administered and irradiated mice, only 2.1+/-0.4 apopto
tic cells per crypt was observed. In vitro and in vivo data obtained in thi
s study showed that DTT reduced radiation-induced damages and it seems that
the possible radioprotective mechanisms of action of DTT are prevention of
chromosome aberration.