Promotion by substance P of gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in Wistar rats

The effects of prolonged administration of neuropeptide substance P (SP) on gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and on the labeling index of gastric mucosa were investigated in Wistar rats. Rats received subcutaneous injections of 12 μg/kg body weight of SP every other day after 25 weeks of oral treatment with MNNG. Long-term administration of SP significantly increased the incidence of gastric cancers in week 52. However, it did not affect the histological type and depth of involvement of gastric cancers. SP also caused a significant increase in the labeling index of the antral and fundic epithelial cells in week 52. These findings indicate that SP promotes gastric carcinogenesis and suggest that this effect may be related to its stimulation of antral epithelial cell proliferation.