Effect of X irradiation on secondary palate development in mice

The mechanisms whereby X irradiation induces palatal clefting were investigated 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 radiation, 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 with each other. On gestational day 13.5 after labeling, bromodeoxyuridine-positive cells were sparse and apoptotic cells were abundant in the irradiated shelves. To prevent secondary effects of irradiation from the injured maternal body, fetal palatal explants were immediately transferred to an organ culture system after X irradiation in utero. The incidence of palatal clefting 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 cell proliferation and induced apoptosis, resulting in small-volume palatal shelves that could not fuse with each other. The organ culture data also indicated that 4 Gy of irradiation appears to produce its effects both by a direct action on the fetus and indirectly by affecting the metabolism of the pregnant dam.