Non-Neoplastic and Neoplastic Thyroid Disease in Beagles Irradiated during Prenatal and Postnatal Development

Abstract

To evaluate the lifetime hazards of exposure to ionizing radiation, 1,680 beagles received whole-body exposures to 60Co gamma rays or sham exposures during development. Eight groups of 120 dogs each received mean doses of 16-18 or 81-88 cGy at 8, 28 or 55 days of gestation, or at 2 days after birth. One group of 120 dogs received a mean of 83 cGy at 70 days of age and one group of 240 dogs received a mean of 81 cGy at 365 days of age. Sham irradiations were given to 360 controls. Sexes were equally represented. In 1,343 dogs allowed to live out their life span, heritable lymphocytic thyroiditis with hypothyroidism was a major contributor to mortality. Irradiated dogs had a decreased risk for hypothyroidism, a finding that was surprising and not easily explained. Of the 1,343 life-span dogs, those exposed as neonates at 2 days of age or as juveniles at 70 days of age had evidence for an increased risk for thyroid follicular cell neoplasia. Hypothyroid dogs had a significantly increased risk for thyroid neoplasia, including greater risk for carcinomas, but no evidence of a greater sensitivity to radiation-induced tumors. In dogs with normal thyroid function irradiated at 2 or 70 days of age there was increased risk for benign and malignant follicular cell neoplasms, including multiple neoplasms. No difference between sexes was noted. These findings related to age sensitivity in the dog were consistent with the high risk for radiogenic thyroid neoplasia in humans after exposure during early childhood.

A Screening Study of Thyroid Cancer and Other Thyroid Diseases among Individuals Exposed in Utero to Iodine-131 from Chernobyl Fallout

“…In irradiated fetal lymphocytes from 40-yr-old survivors of in utero A-bomb exposure, Ohtaki et al (33) observed no evidence of a higher prevalence of chromosome translocations, except perhaps at very low doses. There have been a few animal studies, the most noteworthy a study of beagles irradiated both in utero and postnatally (34), with increased risk for thyroid disease found only among those who received radiation postnatally.…”

Canine Thyroid Tumors and Hyperthyroidism

“…In dogs the only known risk factors for thyroid neoplasia are hypothyroidism due to thyroiditis (Benjamin et al, 1996) and ionizing radiation (Benjamin et al, 1997). Studies in humans have suggested an association between thyroid neoplasia and (1) iodine deficiency or excess, (2) chronic excesses in thyroid-stimulating hormone (also known as thyrotropin; TSH) secretion, (3) ionizing radiation, and (4) gene abnormalities and oncogene expression.…”

Heritability of hypothyroidism in the Finnish Hovawart population

“…Hypothyroidism is mainly caused by lymphocytic thyroiditis or idiopathic thyroid atrophy [ 6 ]. Lymphocytic thyroiditis is considered as an autoimmune disorder [ 9 , 10 ] and has a hereditary predisposition [ 2 , 7 , 11 ]. It also has been suggested that the disease may be influenced by a major gene [ 11 ].…”

“…Lymphocytic thyroiditis is considered as an autoimmune disorder [ 9 , 10 ] and has a hereditary predisposition [ 2 , 7 , 11 ]. It also has been suggested that the disease may be influenced by a major gene [ 11 ]. Lymphocytic thyroiditis is known to be associated with the major histocompatibility complex (MHC) or dog leukocyte antigen (DLA) system class II allele [ 5 , 12 – 14 ].…”

“…However, the genetic background of hypothyroidism has not been studied extensively, and only a few heritability estimates have been reported. Benjamin et al [ 7 ] obtained a moderate estimate of heritability (0.3) based on 276 laboratory Beagle dogs with 16 % diagnosed as hypothyroid, and a slightly smaller estimate (0.2) based on over 1000 laboratory Beagles in an experiment designed to study the effect of radiation on the risk of hypothyroidism [ 11 ]. The heredity estimates presented here for hypothyroidism in the Finnish Hovawart population are based on a pedigree analysis of 107 dogs affected with hypothyroidism and 4846 unaffected dogs.…”