1995 Volume 8 Issue 4 Pages 417-426
To determine whether promotion of thyroid proliferative lesion development is more effectively achieved by increasing dose treatment with a goitrogen than with continuous administration, male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN, 2, 800mg/kg body weight, single s.c. injection) were given water containing 0.1% sulfadimethoxine (SM) for 20 weeks (group 1), 0.025, 0.05, and 0.1 of SM for 8, 4 and 4 weeks, respectively (group 2), and 0.025, 0.05, 0.1 and 0.2% of SM for 8, 4, 4 and 4 weeks, respectively (group 3). Control rats (group 4) were maintained without further treatment for 20 weeks after DHPN-initiation. Both absolute and relative thyroid weights in group 3 were significantly increased as compared to group 1. Serum T3 and T4 levels were significantly decreased in groups, 1, 2, and 3 as compared to group 4, the serum T4 level in group 3 being also significantly decreased as compared to the group I value. Serum TSH was significantly elevated in groups 1, 2, and 3 and higher in the latter two cases than in group 1. The numbers of follicular cell hyperplasias in groups 2 and 3 and adenomatous tumors in group 3 were also significantly increased, as compared to group 1, along with BrdU labeling indices for follicular cells, hyperplasias, and adenomatous tumors. The present results indicate that step-wise increasing dose treatment with SM enhances production of thyroid proliferative lesions and their cell proliferative activity to a greater extent than continuous treatment despite a lower total intake and suggest that this approach may be more sensitive for detection of thyroid tumor promoters in rat thyroid two-stage carcinogenesis models.
