Effect of X irradiation on secondary palate development in mice

The mechanisms whereby X irradiation induces palatal clefting were investig ated in vivo and in an in vitro organ culture system. When pregnant mice at day 12.5 of gestation were exposed to a 4-Gy dose of whole-body X radiatio n, the incidence of palatal clefting in their offspring was 91%, The volume of the irradiated palatal shelves was too low for them to make contact wit h each other. On gestational day 13.5 after labeling, bromodeoxyuridine-pos itive cells were sparse and apoptotic cells were abundant in the irradiated shelves, To prevent secondary effects of irradiation from the injured mate rnal body, fetal palatal explants were immediately transferred to an organ culture system after X irradiation in utero. The incidence of palatal cleft ing was 24%, much lower than the incidence in vivo. The addition of 10(-4) M of dexamethasone to the culture medium increased the incidence of palatal clefting to 56%. These findings indicated that X irradiation inhibited cel l proliferation and induced apoptosis, resulting in small-volume palatal sh elves that could not fuse with each other. The organ culture data also indi cated that 4 Gy of irradiation appears to produce its effects both by a dir ect action on the fetus and indirectly by affecting the metabolism of the p regnant dam. (C) 2000 by Radiation Research Society.