Neoplasia and Internal Environment

Bielschowsky, F

doi:10.1038/bjc.1955.7

Cited by 85 publications

(18 citation statements)

References 61 publications

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“…The striking summation effect in carcinogenesis of radiation followed by methylthiouracil was noted previously (Doniach, 1950) and compared with the carcinogenic summation effect of acetylaminofluorene and goitrogens first demonstrated by Bielschowsky (1944). The added interest in the present experiment is that the effective dosage of radiation from I131 is equivalent to as little as 1100 rads X rays.…”

Section: Carcinogenic Action Of Irradiation and Summation With Thyroisupporting

confidence: 74%

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

Doniach¹

1957

Br J Cancer

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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

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Section: Carcinogenic Action Of Irradiation and Summation With Thyroisupporting

confidence: 74%

“…alone leads eventually to carcinoma formation in the rat's thyroid (Bielschowsky, 1955;Axelrad and Leblond, 1955). The excess T.S.H.…”

Section: Discussionmentioning

confidence: 99%

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

Doniach¹

1957

Br J Cancer

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“…10,15 Animal studies had clearly shown the role of chronic stimulation of the thyroid by TSH and goitrogenic diets in promoting thyroid hyperplasia and later neoplasia. 16,17,25 In spite of this, there is no acceptable evidence of malignancy in dyshormonogenetic goiters where there are high and sustained TSH levels. 26 However, TSH is suppressed in Graves' disease, so the stimulation of thyroid is not through TSH, but probably through circulating thyroid stimulating antibodies (TSAB).…”

Section: Discussionmentioning

confidence: 99%

Functioning Thyroid Carcinoma Occurring in Graves' Disease: A Report of One Case and Review of the Literature

Saadeh

Abu-Farsakh

1995

Ann Saudi Med

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“…Rich historical literature is also valuable (26)(27)(28)(29)(30)(31)(32)(33) (25,43). Normal cell division in the thyroid seems to be affected by an interplay among several mitogenic factors, namely TSH, insulin-like growth factor 1 (IGF-1), insulin, epidermal growth factor (EGF), and possibly fibroblast growth factor (FGF).…”

Section: Overview Of Thyroid Carcinogenesismentioning

confidence: 99%

Risk Assessment of Thyroid Follicular Cell Tumors

Hill¹,

Crisp²,

Hurley³

et al. 1998

Environmental Health Perspectives

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Thyroid folliclar celi tumor arise in rodents from mutations, perturbations of thyroid and pituitay hormone status with increased sution of thyroid cell growth by thyroid-stimulating hormone (TSH), or a combination of the two. The only kown human thyroid carcinogen is ionizing radiation. It is not known for certain whether chemicals that affect thyroid cell growth lead to human thyroid cancer. The U.S. Environmental Protection Agency applies the following science policy positions: 1) chemical induced rodent thyroid tumors are presumed to be relevnt to humans; 2) when interspecies information is lacking the default is to asme comparble carcinogenic senitivity in rodents and humans; 3) adverse rodent noncancer thyroid effe due to chemically induced thyroid-pituity disruption are presumed to be relevant to humans; 4) linear dose-response considerations are applied to thyroid cancer induced by chemical substaces that either do not disrupt thyroid functioning or lack mode of action information; 5) nonlinear thyroid cancer dose-response considerations are applied to chemicals that reduce thyroid hormone levels, increase TSH and thyroid cell division, and are judged to lack mutanic acivity, and 6) nonlinear conideions may be applied in thyroid cancer dose-response assessments on a caseby-case basis for chemicalls that disrupt thyroid-pituitary functioning and demonstrate some mutagenic activity. Required data for risk asessment purposes is mode of action information on mutgenicity, increases in follicular cell growth (cell size and number) and thyroid gland weight, thyroid-pituitary honrones, site of action, correlations between doses producing thyroid effects and cancer, and reversibility of effet when dosing ceases. Key won iodide pump, microsomal enzyme induction, 5'-monodeiodinase, ris assessment, thyroid follicular cell tumors, thyroid hormone (T4, T3), thyroid p ida, throid-smulating hormone (TSH), UDP glucuronosyl trnsferase.

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Neoplasia and Internal Environment

Cited by 85 publications

References 61 publications

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

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

Functioning Thyroid Carcinoma Occurring in Graves' Disease: A Report of One Case and Review of the Literature

Risk Assessment of Thyroid Follicular Cell Tumors

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