Large amount of vitamin A has no major effects on thyroidal hormone synthesis in two-stage rat thyroid carcinogenesis model using N-bis(2-hydroxypropyl)nitrosamine and thiourea.
In our previous investigation, which focused on two-stage carcinogenicity in the thyroid, rats were administered N-bis(2-hydroxypropyl)nitrosamine (DHPN), followed by thiourea (TU) over an experimental period of 19 weeks. Simultaneous treatment with a high level of vitamin A (VA) enhanced the induction of proliferative lesions that originated from the thyroidal follicular epithelium. To examine whether hormone synthesis in the thyroid could be inhibited by simultaneous treatment with a large amount of VA and TU, all of the rats were initially given a single subcutaneous injection of 2,800 mg DHPN/kg followed by a supply of 0% TU + 0% VA (DHPN only, control group), 0.2% TU in their drinking water (DHPN/TU group), 0.1% VA in their diet (DHPN/VA group), or 0.2% TU + 0.1% VA (DHPN/TU + VA group) during an experimental period of 4 weeks. Results obtained indicate that the iodine uptake and organification, namely iodination of tyrosine residue in thyroglobulin, of the thyroid, were significantly decreased in the DHPN/TU group compared to the DHPN control group. The variation in these values was attributable to the inhibitory effect of TU upon thyroid hormone synthesis. Results obtained from the DHPN/TU + VA and DHPN/TU groups were comparable. Therefore, the possibility that modification of hormone synthesis contributes to the enhancing effect of simultaneous treatment with a large amount of VA on thyroidal tumor induction by TU is considered to be very minimal.
Takegawa
K
K
Safety Evaluation Laboratory, Yoshitomi Pharmaceutical Industries Co., Ltd., Hyogo, Japan.
Sakamori
M
M
Koremoto
M
M
Yamada
T
T
Takagi
S
S
Takeuchi
M
M
Yanai
T
T
Masegi
T
T
Mitsumori
K
K
D000236:Adenoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D004357:Drug Synergism; D006965:Hyperplasia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007455:Iodine / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D009602:Nitrosamines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013890:Thiourea / Q000633:toxicity*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013963:Thyroid Hormones / Q000096:biosynthesis*; D013964:Thyroid Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D014801:Vitamin A / Q000494:pharmacology*
D002273:Carcinogens; D009602:Nitrosamines; D013963:Thyroid Hormones; D014801:Vitamin A; C012457:diisopropanolnitrosamine; D007455:Iodine; D001973:Bromodeoxyuridine; D013890:Thiourea