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

Abstract

The specificity of copromotion effects of caffeine with known goitrogenic factors on thyroid carcinogenesis was examined in rats pretreated with Nbis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided into 8 groups, each consisting of 10 animals, and received a single sc injection of 2,800 mg/kg DHPN. From one week after the DHPN initiation, they were given basal diet, iodine deficiency (ID) diet, 500 ppm phenobarbital (PB) solution or 1,000 ppm sulfadimethoxine (SDM) solution with or without 1,500 ppm caffeine feeding for 12 weeks. The caffeine, PB, SDM, and ID treatments significantly ( p < 0.05 or 0.01) increased the relative thyroid weights, and the increases with PB or ID were further ( p < 0.05 or 0.01) enhanced in combination with caffeine. SDM drastically promoted thyroid carcinogenesis in association with increased serum TSH levels regardless of the caffeine treatment. Thyroid follicular carcinomas and adenomas were more frequently observed in the additional caffeine groups than in the ID alone groups. The incidence and multiplicity of focal thyroid follicular hyperplasias in the ID-treated groups were significantly ( p < 0.05 and 0.01) elevated in the case of combination with caffeine. Increases in serum TSH levels with PB or ID were also further enhanced in combination with caffeine. Serum thyroid hormone levels were significantly ( p < 0.01) decreased by SDM but significantly ( p < 0.05 or 0.01) increased by caffeine, PB or ID. Our results clearly indicate that dietary caffeine at a high dose of 1,500 ppm interacts with ID, but neither SDM nor PB, to promote rat thyroid carcinogenesis although the combined caffeine + PB treatment somewhat affected thyroid weights as well as thyroid hormone levels.

Thyroid Pathological Consequences Induced by Caffeine in Female Rats

“…This study denote that caffeine causes significant reduction in thyroid function in all treated groups compared to control group with main reduction in T3, however, non-significant variations in TSH, T4 levels were detected. This result opposes with results of other studies which state that thyroid hormones are increased by use of caffeine 7,8,9 . Another researcher states that consumption of caffeine in high doses cause significant increase in T3 and T4 with non-significant change in TSH level 10 and clarified that may be due to caffeine inhibition of c-AMP breakdown by blocking the activity of phosphodiesterase enzyme resulting an elevated c-AMP level which is necessary for proliferation and secretion of thyroid follicles 11,12,13 .…”

Promoting effects of carminic acid-enriched cochineal extracts on capsular invasive thyroid carcinomas through targeting activation of angiogenesis in rats

“…Serum TSH concentration in the present study was >100-fold lower than that in the previous studies (Mitsumori et al, 1995;Son et al, 2004;Imai et al, 2009). This gap is due to the difference in the detection system of TSH.…”

Lac color inhibits development of rat thyroid carcinomas through targeting activation of plasma hyaluronan-binding protein

“…However, this level was still rather high and at least 13-fold than that in adult F344 rats without promoter treatment, ranging from 5 to 7 ng/mL. 30–32 Moreover, the TSH reduction was in contrast to the strong suppression of the formation of TN-C-positive foci as well as of capsular inflammation and fibrosis by LC treatment at this time point. Considering apparent induction of tumor-promoting activity even with a serum TSH concentration twice that of unpromoted animals, 31 the serum TSH concentration was rather high even after LC treatment to be sufficient for inducing strong tumor-promoting activity in the present study.…”