Comparison of the Carcinogenic Effect of X-Irradiation with Radioactive Iodine on the Rat's Thyroid

Abstract

RATS injected with 30 ,C radioactive iodine (1131) and kept on methylthiouracil for the succeeding 15 months show adenomatous replacement of the thyroid gland and occasional thyroid carcinomas; unirradiated controls treated with methylthiouracil for 15 months develop a moderate number of adenomas but no carcinomas (Doniach, 1950 and1953). The radiation dose, which is comparable to that used in the treatment of Graves' disease, varies extremely widely within the rat's thyroid gland. The following experiment is an attempt to find out whether radiation in the lower part of the dosage range, given before the goitrogenic treatment, is effective or not in initiating carcinogenesis. Dosage uniformity within the thyroid was obtained by irradiation with X rays. Comparison was made between the carcinogenic effect of 30 ,C 1131 with a single exposure of the thyroid to 1100 rads X rays. This dose of X rays was chosen because we had found previously in a biological assay that it was comparable with 30 jC 1131 in its potency to inhibit the response of the rat's thyroid to a goitrogenic challenge given 4 months after the irradiation (Doniach and Logothetopoulos, 1955;Abbatt, Doniach, Flanders and Logothetopoulos, 1957). MATERIAL AND METHODSOne hundred and sixty animals were used. They were black and white hooded male and female rats from a closed colony of the hooded Lister strain, fed on "Research" rat cubes with additional bread and greens. The 4-methyl-2-thiouracil (B.D.H.) was given as a saturated solution in the drinking tap water, made up once weekly by suspending 1 g. of the compound in each litre of water. The radioactive iodine, 1131, was injected intraperitoneally, carrier free as iodide in 1 ml. water. For X-irradiation deep anaesthesia was temporarily induced with ether vapour followed by intramuscular injection of 2.5 mg. Largactil (Chlorpromazine). The anaesthetized animals were immediately confined in a special holder and irradiated as described by Abbatt et al. (1957), the site of the thyroid having been marked with ink on the skin of the front of the neck. The X ray beam was defined by a perforated lead shield to a diameter of 1.3 cm. applied to the central surface of the neck immediately over the thyroid and portion of trachea between the 2 lobes. The physical factors were; 190 kV. X rays, 6 m.a., filtered by imm. Cu. and 1 mm. A1. The dose rate, taking the centre of the thyroid to be 8 mm. below the skin surface, was 150 rads/min. measured by means of a BD2 type condenser ionization chamber with the small air voume placed at this depth. 1100 rads were delivered to the thyroid of each rat. The irradiation was carried( out by P. Howard Flanders .of the Experimental Radiopathology Research Uniit

131I Induced Hematological Alterations in Rat Blood: Protection by Zinc

“…treatments [2], the use of 131 I has been met with several objections, the most significant of which is the question of oxidative stress and carcinogenicity [3,4]. The damage to the thyroid gland from deposition of radioiodine has often been described in literature [5][6][7].…”

Correlation of dose of x-radiation to the rat thyroid gland with degree of subsequent impairment of response to goitrogenic stimulus.

“…Doses of 500 to 2000 rads X-rays to the thyroid have been showin to induce adenomas and carcinomas of the thyroid in rats (Doniach, 1956;Frantz et al, 1957;Lindsay et al, 1961). It is of interest, and pertinent to the analysis of the carcinogenic action of radiation, to assess other biological effects oIn the thyroid of this order of radiation.…”

Cases of Carcinoma of Thyroid following Iodine-131 Therapy for Hyperthyroidism

“…Lindsay et al [8] found that a higher incidence of thyroid malignancy in rats followed rela tively small doses of 1311. X-irradiation doses of only 10 rads are of significant risk to children [2] but the dose of X-irradiation required for carcinogenesis is much lower than for irradiation by 1311 [9], Doniach [10] has proposed that both ionising irradiation and a non-specific stimulus to thyroid growth are needed to induce thyroid cancer and that the growth stimulus is naturally present in children. The thyroidstimulating immunoglobulins which are widely be lieved to be responsible for the hyperthyroidism of Graves' disease might also provide this stimulus to growth.…”