T. Shimo et al., TIME-COURSE OBSERVATION OF THYROID PROLIFERATIVE LESIONS AND SERUM TSH LEVELS IN RATS TREATED WITH THIOUREA AFTER DHPN INITIATION, Cancer letters, 85(2), 1994, pp. 141-149
Time course changes in serum TSH and quantitative data for thyroid pro
liferative lesions in male F344 rats administered N-bis(2-hydroxypropy
l)nitrosamine (DHPN: 2000 mg/kg body weight, single s.c. injection) fo
llowed by 0.1% thiourea (TU), were assessed at weeks 1, 2, 4, 8, 12 an
d 16 of treatment. The serum T4 level in the TU group was markedly dec
reased at week 1 and remained significantly lowered throughout the exp
eriment. Serum TSH levels, in contrast, were elevated up to a peak at
around week 4 with a return to the normal range at week 12. Thyroid we
ights in the TU group were increased significantly in a treatment peri
od-dependent manner. Histopathologically, marked hypertrophy of thyroi
d follicular cells occurred at the early stage of TU treatment. Prolif
erative lesions, such as hyperplasia and adenomas, occurred from weeks
2 and 4, respectively, and increased with the later treatment period.
The cell proliferative activity of follicular cells, assessed by BrdU
incorporation, was high until week 2, but then returned to normal. Th
e initially appearing hyperplasias and adenomas were characterized by
marked proliferation but this also greatly decreased at later stages w
hen TSH was no longer elevated. The results of our study thus suggest
that a high serum TSH level plays an important role in the early phase
of thyroid tumorigenesis and 8 weeks treatment with test substances i
s sufficient for detection of thyroid tumor promoter potential in two-
stage thyroid carcinogenesis models.