Effect of rat thyroid proliferative lesion development by intermittent treatment with sulfadimethoxine.

To determine whether production of thyroid proliferative lesions would be enhanced by intermittent rather than continuous treatment with a goitrogen, male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN, 2800 mg/kg body weight, single s.c. injection) were given water containing 0.1% sulfadimethoxine (SM) for 20 weeks (group 1) or 0.1% SM for the first 8 weeks followed by 2 cycles consisting of 2 weeks withdrawal and 4 weeks retreatment with 0.1% SM (group 2). Control rats (group 3) were untreated for 20 weeks after the DHPN initiation. Serum T3 and T4 levels were significantly decreased in groups 1 and 2 compared to group 3. Serum thyroid stimulating hormone level was significantly increased in all treated groups compared to group 3. The numbers of follicular cell hyperplasias were significantly increased in group 2 compared to group 1. BrdU labeling indices for follicular cells and hyperplasias were also significantly elevated in group 2 compared to group 1. Electron microscopic examination of thyrotrophs in the anterior pituitary in groups 1 and 2 revealed dilated rough ER cisternae with intracisternal dense granules. The number of intracytoplasmic secretory granules in group 2 was moderately decreased compared to group 1. Therefore, the results of the present study suggest that it may be possible to enhance production of thyroid neoplastic lesions by intermittent treatment.