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

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In our previous investigation, which focused on two-stage carcinogenicity in the thyroid, rats were administered N-bis(2-hydroxypropy1)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.