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To investigate the effects of nonuniform irradiation on the small intestine, we prepared 24 dogs for continent isoperistaltic ileostomies under aseptic surgical conditions and general anesthesia. After a 3-week recovery period, the ileum was catheterized with a fiberoptic endoscope to observe the intestinal mucosa and to harvest mucosal biopsies. The baseline macroscopic and microscopic appearance of the intestinal mucosa was determined. Two weeks later, the ileum was catheterized with a 100-cm soft tube containing 40 groups of three thermoluminescent dosimeters placed at equally spaced intervals, and a dose of either 4.5, 8, 10, 11, or 15 Gy 60Co gamma rays was delivered to the right abdomen (nonuniform exposure). This method allowed a direct and precise assessment of the dose received at 40 sites located in the 100-cm intestinal segment. The intestinal mucosa was again evaluated 1, 4, and 6 days after irradiation. All animals exposed to 4.5 and 8 Gy survived, whereas none survived after 11 and 15 Gy. After exposure to 10 Gy, 60% of the animals died within 4-6 days and 40% survived with symptoms associated with both the intestinal and the hematopoietic syndromes. Crypt cell necrosis, blunting of villi, and reduction of the mucosal lining increased between 1 and 4 days after irradiation, and mucosal damage was correlated with intraintestinal dosimetry at Day 6. The granulocyte counts at Day 4 were significantly lower than baseline level in animals that died within 4-6 days but not in survivors. The present model appears to be realistic and clinically relevant, allowing the concurrent study of the intestinal and hematopoietic effects of high-dose nonuniform irradiation similar to that received by patients during radiation therapy as well as by radiation accident victims.

Immunologic responses were studied in beagle dogs following prenatal (35 days gestation) irradiation to evaluate the effects of ionizing radiation on the developing immune system. Each dog received 1.5 Gy 60Co - irradiation or sham irradiation. Prenatally irradiated dogs exhibited a significant reduction in primary humoral antibody responses to inoculated sheep red blood cells, a T-dependent antigen, and a concurrent decrease in T-helper lymphocyte subpopulations in the peripheral blood at 3 to 4 months of age. Similarly, irradiated fetuses have been shown to have defects in epitheliostromal development of the thymus. It is suggested that the postnatal

Hematologic and hematopoietic responses were evaluated in beagle dogs following a single prenatal (35 days gestation) or neonatal (10 days postpartum) exposure to 1.5 Gy /sup 60/Co gamma radiation. Hematopoiesis was studied by the in vitro culture of bone marrow granulocyte-macrophage progenitors (CFU-GM). Prenatally irradiated dogs exhibited a progressive, significant reduction in CFU-GM which was accompanied by decreases in peripheral blood leukocytes up to 24 weeks of age. Dogs which were neonatally irradiated also demonstrated a significant reduction in CFU-GM which was accompanied by significant alterations in peripheral white and red blood cell parameters. This was transient, however, and these dogs showed partial recovery of CFU-GM and hematologic parameter by 24 weeks of age. The persistent CFU-GM deficit in prenatally irradiated dogs suggests a relatively greater sensitivity of fetal marrow as compared to neonatal bone marrow for long-term damage by ionizing radiation.