Enhancing effects of dietary salt on both initiation and promotion stages of rat gastric carcinogenesis.
Relatively short-term treatment (8 weeks) of rats with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/l) was shown to adequately initiate gastric carcinogenesis when 10% NaCl was simultaneously administered in the diet. Utilizing this MNNG plus high salt diet as the initiation stage of a two-step protocol, it was also established that subsequent dietary administration of NaCl (10% of the diet) for 32 weeks tended to enhance tumor development in the glandular stomach. Similar tumor promoting activity was demonstrated for other mucosal damaging agents, such as potassium metabisulfite and formaldehyde. Biological changes of the gastric mucosa were examined after chronic administration or a single oral intubation of NaCl. Morphological lesions observed included diffuse mild erosions, atrophy of the glands, and hyperplasia of the foveolar epithelium when given 10% NaCl diet chronically. After a single oral intubation of NaCl, increased tritiated thymidine labeling index and ornithine decarboxylase (ODC) activity were observed in both pyloric and fundic mucosa. No remarkable effects of NaCl were observed on the forestomach or duodenal mucosa. These results suggest that NaCl exerts an enhancing effect at both initiation and promotion steps within the two stage model system of the gastric carcinogenesis, and that these effects of NaCl are possibly related to its mucosal damaging activity.
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006651:Histocytochemistry; D006965:Hyperplasia; D008297:Male; D008769:Methylnitronitrosoguanidine; D008854:Microscopy, Electron; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D051381:Rats; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D013274:Stomach Neoplasms / Q000139:chemically induced*
D008769:Methylnitronitrosoguanidine; D012965:Sodium Chloride; D004247:DNA; D009955:Ornithine Decarboxylase