Promoting effect of large amounts of vitamin A on cell proliferation of thyroid proliferative lesions induced by simultaneous treatment with thiourea.
In order to examine modifying effects of simultaneous treatment with large amounts of vitamin A (VA) and thiourea (TU) on the thyroid tumorigenesis in rats, male F344 rats were initiated with N-bis(2-hydroxypropyl)nitrosamine (2800 mg/kg body weight, single s.c. injection), and starting 1 week later received diet containing 0.1% VA (VA group), drinking water containing 0.2% TU (TU group), 0.2% TU + 0.1% VA (TU + VA group) or tap water/basal diet (control group) for 19 weeks. Serum T3 and T4 in the TU and TU + VA groups were significantly decreased as compared to the control group, while serum TSH levels were remarkably increased. The ratios of T3 and T4 decrease and TSH increase in the TU + VA group were remarkably more pronounced than in the TU group. Thyroid neoplastic lesions were only induced in the TU and TU + VA groups. The multiplicity of intracapsular follicular cell proliferative foci in the TU + VA group was significantly increased as compared to the TU group value. Cell proliferation of hypertrophic and subcapsular follicular cells, as well as in hyperplasias, and neoplasias with adenomatous growth pattern was significantly higher in the combined treatment case than after TU alone. In the liver, centrilobular hypertrophy of hepatocytes was seen in the TU and TU + VA groups, this being especially marked in the latter group. In the combined group case the affected cells were strongly positive for GST-P antibody binding. The results of the present study suggest that cell proliferation of thyroid follicular cell proliferative lesions in rats is enhanced by strong TSH stimulation with simultaneous treatment of TU and large amounts of VA.
Mitsumori
K
K
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
Onodera
H
H
Takahashi
M
M
Shimo
T
T
Yasuhara
K
K
Takegawa
K
K
Takahashi
M
M
Hayashi
Y
Y
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D008297:Male; D009602:Nitrosamines / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D013890:Thiourea / Q000633:toxicity*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000139:chemically induced / Q000473:pathology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014801:Vitamin A / Q000494:pharmacology*
D002273:Carcinogens; D009602:Nitrosamines; D014284:Triiodothyronine; D014801:Vitamin A; C012457:diisopropanolnitrosamine; D013972:Thyrotropin; D013890:Thiourea; D013974:Thyroxine