Mechanistic Data and Risk Assessment of Selected Toxic End Points of the Thyroid Gland

Abstract

Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis, secretion, and metabolism of thyroid hormones. This includes (a) inhibition of the iodine trapping mechanism, (b) blockage of organic binding of iodine and coupling of iodothyronines to form thyroxine (T 4 ) and triiodothyronine (T 3 )

Specificity of Co-Promoting Effects of Caffeine on Thyroid Carcinogenesis in Rats Pretreated with N-Bis(2-hydroxypropyl)nitrosamine

“…SDM exerts a goitrogenic effect by inhibition of TPO, which catalyzes a reaction essential to thyroid hormone synthesis, resulting in marked decrease in circulating T 3 and T 4 levels and compensatory increase in TSH levels as well as thyroid weights in rats (Hill et al, 1989;Capen, 1997). In the present study, SDM treatment in fact reduced serum T 3 and T 4 levels, and consequently increased serum TSH levels.…”

“…The other, resulting from exposure to non-genotoxic chemicals, involves the negative feedback system of the hypothalamus-pituitarythyroid. Decreased circulating T 3 or T 4 levels due to disruption of thyroid function increase TSH, by which prolonged stimulation of follicular epithelium results in thyroid neoplasia (Hill et al, 1989;McClain, 1992;Capen, 1997). Many factors may contribute to decreases in circulating thyroid hormone levels.…”

“…Many factors may contribute to decreases in circulating thyroid hormone levels. For example, inhibition of iodine transport into the thyroid, iodine oxidation, organification defects due to inhibition of thyroid peroxidase (TPO), inhibition of thyroid hormone secretion or hormone inactivation by hepatic microsomal enzymes such as T 4 -UDP-GT (Hill et al, 1989;Capen, 1997).…”

Lack of Modifying Effects of Environmental Estrogenic Compounds on the Development of Thyroid Proliferative Lesions in Male Rats Pretreated with N‐Bis(2‐hydroxypropyl)nitrosamine (DHPN)

“…The fact that development of thyroid proliferative lesions initiated by pretreatment with DHPN was obviously increased by SDM validates the experimental model used in the present study. It is well documented that sulfonamides including SDM exert a goitrogenic effect by inhibition of thyroperoxidase, resulting in marked decreases in circulating T 3 and T 4 and consequent compensatory increases in TSH and thyroid weight in rats. 3) Epidemiological studies suggest that a diet rich in soy products reduces the risk of several cancers, notably those of the prostate, 10) breast, 11) uterus 12) and stomach.…”

“…These compounds, including several flavonoids, isoflavones, lignans, phytosterols and coumestans, exert antiestrogenic effects by competitive binding to estrogen receptors. 9) Several 3 To whom correspondence should be addressed. E-mail: son@nihs.go.jp epidemiological studies have suggested that soy products and isoflavones may be protective against breast and other hormone-related cancers in humans.…”