Bile reflux: a possible cause of stomach ulcer in nontreated mutant mice of W/WV genotype.

The chronic antral ulcer developed spontaneously in (WB X C57BL/6)F1-W/WV mice. Natural history of the ulcer was investigated to make clear the mechanisms involved in the development of ulcer in this mutant mouse. Although no histopathologic abnormalities of the stomach were detected at the fifth day after birth, erosions developed at the tenth day and the severity of the ulcerative lesions advanced with age. Antral pH of the W/WV mice was higher than that of the congenic +/+ mice, and the content of gastrin in the glandular stomach of the former was lower than that of the latter. Therefore, hyperacidity cannot be the cause of the ulcer in the W/WV mice. Bilirubin was demonstrable in the stomach contents of the suckling W/WV mice. After subcutaneous injection of [35S]sulfobromophthalein, the 35S radio-activity in the stomach contents of the 10-day-old W/WV mice was about 40 times as great as that observed in the +/+ littermates. As the peak of the bile reflux occurred shortly before the development of obvious ulcer that penetrated beyond the muscularis mucosae, the bile reflux could be a cause rather than a result of the ulcer.