Enhancement by thyroxine of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats

Abstract

25 weeks, the rats received s.c. injections of T4 (0.2 jug kg-') 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.Thyroid hormones have important regulatory roles in the morphology and biochemistry of gastrointestinal mucosal cells (Hernandez et al., 1988). Long-term T4 administration increased the mitotic activity of the fundic 'stem' cells of the stomach and basal and secretagogue-stimulated acid secretion via its effect on parietal cell mass (Adeniyi & Olowookorun, 1989). We recently found that prolonged administration of T4 significantly increased the incidence of rat colon tumours induced by azoxymethane (Iishi et al., 1992). These findings suggest that T4 might influence gastric carcinogenesis. Therefore, in the present work, we examined the effect of treatment of rats with T4 on the development of gastric cancers in rats. Materials and methods AnimalsSixty 6-week-old male Wistar rats (SLC, Shizuoka, Japan) were used in this study. (Siegel, 1956). Other results were all analysed by one-way analysis of variance with Dunn's multiple comparison (Snedecor & Cochran, 1967;Miller, 1966

Male Predominance of Gastric Cancer among Patients with Hypothyroidism from a Defined Geographic Area

“…Under the assumption of a potential cancer risk being equal in both sexes upon exposure to hypothyroidism, the most reasonable hypothesis is that females exposed to hypothyroidism are less likely to develop GC than males, irrespective of H. pylori infection and other environmental factors, due to some protection by sex hormones. Studies on animal models as well as in humans indicate that estrogen may protect against GC [37,38] and this mechanism may also be operative in perimenopausal females who, in addition to levothyroxine, may resort to replacement hormone therapies to delay menopause. This notion is consistent with the results of clinical trials showing an increased incidence of GC in females treated with tamoxifen, a known anti-estrogen [39].…”

Thyroxin Use Is Associated With Increased Risk of Thyroid Cancer in Patients With Hypothyroidism

“…Lishi et al first reported that thyroxin enhances the carcinogenesis effect of azoxymethane in inducing rat colon adenocarcinoma . Later, the same group determined that thyroxin also enhances the gastric carcinogenesis induced by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine in Wistar rats . Second, thyroxin on its own might stimulate the growth of thyroid cancer cells.…”

“…12 Later, the same group determined that thyroxin also enhances the gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 13 Second, thyroxin on its own might stimulate the growth of thyroid cancer cells. Lin et al reported that thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is antiapoptotic.…”

The Role of Thyroid Hormone Signaling in the Prevention of Digestive System Cancers

“…Not all studies however, suggest a protective role for TH signaling. In one report, gastric cancer incidence in N -methyl- N′ -nitro- N -nitrosoguanidine-treated Wistar rats was increased compared to untreated controls, with administration of T 4 [53]. …”