Relationships between serum thyroid stimulating hormone levels and development of thyroid tumors in rats treated with N-bis-(2-hydroxypropyl)nitrosamine

Abstract

Relationships between serum thyroid stimulating hormone (TSH) levels, carcinogen dose and development of thyroid tumors were studied in Wistar rats of both sexes treated with N-bis-(2-hydroxypropyl)nitrosamine (DHPN). DHPN (210 mg/100 g body wt) was injected i.p. weekly. Wistar rats were used, divided into five groups of males (M1-M5) and five groups of females (F1-F5). M1 and F1 received one injection of DHPN, M2 and F2 two injections of DHPN, M3 and F3 three injections of DHPN, M4 and F4 four injections, and M5 and F5 as control rats received saline vehicle. The resultant incidences of total thyroid tumors were 4% in group M1, 24% in M2, 80% in M3, 76% in M4, 0% in F1, 4% in F2, 20% in F3, 17% in F4 and 0% in M5 and F5. Thus dose dependence for DHPN carcinogenesis was found in both sexes for up to at least three injections of DHPN and in all cases males proved more susceptible than females. Similar results were gained for carcinomas treated separately. A sex difference in DHPN induction of thyroid tumor was thus shown for Wistar rats opposite to that reported to exist in humans. However, no clear relationship between dose of DHPN or incidence of thyroid tumors and serum TSH concentration was evident at the end of the experiment (week 30).

Occupation and thyroid cancer

“…Because occupational exposures are preventable and modifiable and because the incidence of thyroid cancer is increasing, our review suggests that further studies of thyroid cancer and occupational exposures, with sufficient size and high-quality exposure assessment, are warranted. In particular, future studies should focus on exposure agents known to disrupt thyroid homeostasis 25 33 34 36. Understanding whether occupational exposures cause thyroid cancer is important for occupational health implications, and also because it can confer improved insight into thyroid cancer trends.…”

“…The regulation, metabolism and excretion of thyroid hormones have been shown to be altered by a large number of chemicals found in the workplace 29–34. For instance, organochlorine pesticides, polychlorinated biphenyls (PCB), and polybrominated diphenyl ethers (PBDE), as well as anions including perchlorate and nitrate, have been shown in experimental and human studies to decrease serum levels of thyroid hormones and result in increased TSH production 25 33–36. Little is known, however, about the biological pathway between these chemicals, thyroid disruption and thyroid cancer.…”

Comparative proteomic analysis of rat hepatic stellate cell activation: A comprehensive view and suppressed immune response

“…Decreases in available iodide can result in lower production of the thyroid hormones T 3 and T 4 , resulting in increased production of thyroid stimulating hormone (TSH). Based on findings from animal models, chronic TSH stimulation of the thyroid is thought to play a role in thyroid carcinogenesis 13. In addition, nitrate is reduced to nitrite by oral bacteria in human, and nitrite reacts with amines and amides in vivo to form nitrosamines and nitrosamides (collectively known as N‐nitroso compounds [NOC]), potent animal carcinogens.…”

Review of Factors Related to the Thyroid Cancer Epidemic

“…Dietary nitrate is found in cured meats, various types of vegetables, and as contaminant of drinking water, thereby potentially posing bigger public health risks [89, 90]. Nitrate is regarded as a plausible risk factor for thyroid cancer, as it competitively inhibits iodide uptake by the thyroid, potentially affecting thyroid functions [91]. Some epidemiologic evidence is available to demonstrate elevated thyroid cancer risk linked to excess dietary nitrate intake.…”