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 g oitrogen, male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosam ine (DHPN, 2800 mg/kg body weight, single s.c. injection) were given w ater 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 week s withdrawal and 4 weeks retreatment with 0.1% SM (group 2), Control r ats (group 3) were untreated for 20 weeks after the DHPN initiation. S erum T3 and T4 levels were significantly decreased in groups I and 2 c ompared to group 3, Serum thyroid stimulating hormone level was signif icantly increased in all treated groups compared to group 3, The numbe rs of follicular cell hyperplasias were significantly increased in gro up 2 compared to group 1. BrdU labeling indices for follicular cells a nd hyperplasias were also significantly elevated in group 2 compared t o group 1. Electron microscopic examination of thyrotrophs in the ante rior pituitary in groups 1 and 2 revealed dilated rough ER cisternae w ith intracisternal dense granules. The number of intracytoplasmic secr etory granules in group 2 was moderately decreased compared to group 1 , Therefore, the results of the present study suggest that it may be p ossible to enhance production of thyroid neoplastic lesions by intermi ttent treatment.