Abstract
The affects of L-thyroxine (T4) on the incidence and histology of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on the labelling index of gastric mucosal epithelial cells were investigated in Wistar rats. After oral treatment with MNNG for 25 weeks, the rats received s.c. injections of T4 (0.2 microgram kg-1) in depot form every other day until the end of the experiment in Week 52. This long-term treatment with T4 significantly increased the incidence of gastric cancers in Week 52. However, it did not influence the histological type of the gastric cancers. It also caused significant increases in the labelling indices of the fundic and antral epithelial cells. These findings indicate that T4 enhances the development of gastric cancers, and that its effect may be related to its effect in increasing proliferation of gastric epithelial cells.
Highlights
There was no significant difference in the histological types of adenocarcinomas in the two groups: all cancers in Group 1 were very well-differentiated, while in Group 2 very well-differentiated adenocarcinomas were found in 11 (92%) of 12 tumours and the other was well-differentiated
We found that T4 enhanced gastric carcinogenesis induced by MNNG in Wistar rats
Long-term s.c. administration of T4 in depot form significantly increased the incidence of gastric cancer, but had no influence on their histological type at autopsy in Week 52
Summary
Sixty 6-week-old male Wistar rats (SLC, Shizuoka, Japan) were used in this study. They were housed in stainless steel suspended wire mesh cages, under controlled environmental conditions of 12 h light and 12 h darkness, 30-50% humidity, and 21-22'C. The animals were given drinking water containing MNNG (25 ytg ml-'; Aldrich, Milwaukee, WI) for 25 weeks. The stock solution of MNNG was prepared at 1 mg ml1' in deionised water and kept in a cool, dark place and renewed every week. From Week 26, the rats were given normal tap water ad libitum and were randomly divided into two groups of 30 rats each. Injections were given at various sites every other day in a volume of 1 ml kg-' body weight between 2 and 3 p.m
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