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.
Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
J
J
Kanno
C
C
Matsuoka
K
K
Furuta
H
H
Onodera
H
H
Miyajima
A
A
Maekawa
Y
Y
Hayashi
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