Synergism between sodium chloride and sodium taurocholate and development of pepsinogen-altered pyloric glands: relevance to a medium-term bioassay system for gastric carcinogens and promoters in rats.

In an approach to early detection of gastric carcinogens and promoters in an in vivo test system, promotion by sodium chloride (NaCl) and the synergistic effects of NaCl and sodium taurocholate (Na-TC) on development of pepsinogen-altered pyloric glands (PAPG) in rat glandular stomach after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated. A total of 205 male WKY/NCrj rats were divided into 8 groups. Group 1 was given a single dose of MNNG of 160 mg/kg body weight by gastric intubation, and starting 2 weeks later basal diet containing Na-TC for 18 weeks. In addition, 1 ml doses of saturated NaCl solution were given by gastric intubation at weeks 4, 6, 8 and 10. Similarly, group 2 was treated with MNNG and Na-TC, while group 3 animals received MNNG and NaCl. Group 4 was given MNNG alone. Groups 5-8 served as equivalent controls without MNNG initiation. The results revealed significantly enhanced induction of immunohistochemically defined PAPG in the Na-TC + NaCl (P less than 0.001), Na-TC (P less than 0.01) and NaCl (P less than 0.01) treated animals initiated with MNNG. Sodium chloride demonstrated a clear synergistic effect with Na-TC in promoting the development of PAPG, suggesting possible advantage for its use in medium-term in vivo assays for detection of gastric carcinogens and promoters.