Effect of experimental hypochlorhydria on the histological differentiation of adenocarcinomas in the canine stomach.

Hypochlorhydria is considered to be a risk factor for gastric cancer, both clinically and experimentally. In humans, the hypo-acidic condition appears to be closely associated with the development of differentiated-type gastric carcinomas. We investigated relationships between antral pH and histological types of gastric cancer using an animal model. A total of 7.65 g of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was orally administered to male beagle dogs. Subsequently, the dogs were divided into four groups and underwent four surgical interventions designed to create various conditions in the antrum. Antral pH was recorded at the time of killing after an observation period ranging from 16 to 33 months. The number of gastrin-secreting cells (G-cells) was counted after immunohistochemical staining. Carcinomas were found in the antrum of 12 of the 21 dogs that had survived. Although limited doses of ENNG, such as those used in this study, have been reported to produce only undifferentiated adenocarcinomas, differentiated adenocarcinomas were found in seven of these 12 dogs. Antral pH and the number of G-cells were significantly higher in these seven dogs than in the other five dogs, which had developed only undifferentiated adenocarcinomas. Bile inflow showed no significant effect on the development of differentiated adenocarcinomas. Neither atrophic gastritis nor intestinal metaplasia was seen in any of the dogs. These results suggest that the hypo-acidic condition itself may play a role in the development of differentiated adenocarcinomas.