Mortality in Beagles Irradiated during Prenatal and Postnatal Development. II. Contribution of Benign and Malignant Neoplasia

Abstract

To evaluate the lifetime carcinogenic hazards of exposure to ionizing radiation during development, 1,680 beagles received whole-body exposures to 60Co gamma rays or sham exposures. Eight groups of 120 dogs each received mean doses of 15.6-17.5 or 80.8-88.3 cGy in early, mid- or late gestation, at 8, 28 or 55 days postcoitus or at 2 days after birth. Another group of 120 dogs received a mean dose of 82.6 cGy as 70-day-old juveniles and one group of 240 dogs received a mean dose of 81.2 cGy as 365-day-old young adults. Sham irradiations were given to 360 controls. Sexes were equally represented. In 1,343 dogs allowed to live out their life span, neoplasia was a major disease, contributing to mortality in 40% of the dogs. There was a significant increase in benign and malignant neoplasms occurring in young dogs (<4 years old), including fatal malignancies, after irradiation in the perinatal (late fetal and neonatal) periods. The lifetime incidence of fatal neoplasms was also increased in dogs irradiated perinatally. Three malignancies-lymphomas, hemangiosarcomas and mammary carcinomas-accounted for 51% of all fatal tumors. There was an apparent lifetime increase and earlier onset of lymphomas in dogs exposed as fetuses. Fatal hemangiosarcomas were increased in dogs irradiated early and late in gestation. Fatal mammary carcinomas were not increased by irradiation, although non-fatal carcinomas were increased after perinatal exposure. Myeloproliferative disorders and central nervous system astrocytomas appeared to be increased in perinatally irradiated dogs. These data suggest that irradiation in both the fetal and neonatal periods is associated with increased early onset and lifetime cancer risk.

Long-term polyclonal and multilineage engraftment of methylguanine methyltransferase P140K gene-modified dog hematopoietic cells in primary and secondary recipients

“…28 In addition, dogs are more prone to tumors after total body irradiation. 29 Thus, to the best of our knowledge and analysis, this tumor has no association with the genetic modification of the repopulating cells. Generally, the long-term data in this study support the safety of this approach, and the only adverse events appear to be unrelated to the MGMTP140K gene-marked cells.…”

Radiation and breast cancer: a review of current evidence

“…One large experiment, involving lifelong follow-up of 672 female beagles exposed to various radiation doses at different times in the prenatal, perinatal and postnatal periods [74] showed no overall excess of lifetime breast cancer mortality although there was increased risk of non-fatal breast cancer in the subgroup exposed to radiation in the perinatal period [75]. …”

Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium

“…21 Exposure to ionizing radiation seems to be a shared risk factor for development of HSA in dogs. 22 As is true for canine HSA, treatment of human angiosarcomas can be challenging and is frequently unrewarding. 9,11,23 In part, the paucity of effective treatments for endothelial cancers is due to the lack of appropriate reagents to study these diseases.…”