Tumor promoting effect of goitrogens on the rat thyroid.
To evaluate the mechanism of the promoting effect of goitrogens on thyroid tumorigenesis, well-known goitrogens having different pharmacologic action, i.e., thiourea, phenobarbital sodium (PB), potassium thiocyanate (KSCN), and 3,4,5,6-tetrachloro-2',4',5',7'-tetraiodo-fluorescein sodium salt (Rose Bengal B, FD&C Red No. 105) (FR105) were administered to the DHPN-initiated and non-initiated F344 male rats in the drinking water for 25 weeks. Remington's iodine deficient diet (I-def) was fed as a positive control. These goitrogens showed significant tumor promoting effect or promoting tendency on the rat thyroids. According to the changes in thyroid morphology and thyroid-related hormone titers observed in the present study, we proposed to classify goitrogens at least into 2 groups, i.e., iodine deficiency-type promoters and the iodine excess-type promoters. The former contains goitrogens inducing TSH-stimulated diffuse goiter composed of uniform follicles with activated tall follicular epithelial cells, such as thiourea, KSCN and PB, and the latter contains goitrogens inducing colloid goiter composed of a mixture of colloid-rich follicles with flat follicular cells and normal-looking follicles with cuboidal follicular cells, such as FR105. This classification may be useful for the risk assessment of goitrogens.
Kanno
J
J
Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Matsuoka
C
C
Furuta
K
K
Onodera
H
H
Miyajima
H
H
Maekawa
A
A
Hayashi
Y
Y
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D009602:Nitrosamines / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012395:Rose Bengal / Q000494:pharmacology; D013861:Thiocyanates / Q000494:pharmacology; D013890:Thiourea / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood
D013956:Antithyroid Agents; D002273:Carcinogens; D009602:Nitrosamines; D013861:Thiocyanates; D013963:Thyroid Hormones; D012395:Rose Bengal; C012457:diisopropanolnitrosamine; D013972:Thyrotropin; D013890:Thiourea; C009941:potassium thiocyanate; D010634:Phenobarbital