Atrophy of the gastrointestinal mucosa that occurs in pair-fed control rats is not observed in
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD)-treated rats (1). Our objective was to determine if the gastrointestinal trophic
hormone,
gastrin, is involved in the antiatrophy effect of
TCDD on the gut mucosa. Adult male Sprague-Dawley rats treated with 100 micrograms/kg of
TCDD were slightly hypergastrinemic 7 days after dosing and markedly hypergastrinemic 14 days
after treatment whereas pair-fed control rats were normogastrinemic. After 14 days of feed restriction,
atrophy of the oxyntic gland and ileum mucosa occurred in pair-fed control rats but only
atrophy of the ileum mucosa developed in
TCDD-treated animals. The oxyntic gland mucosa of
TCDD-treated rats was protected from mucosa
atrophy as well as from mucosa erosions. The protection against feed restriction-induced
atrophy was demonstrated by measurements of oxyntic gland mucosal height and
DNA and
protein content. Since hypergastrinemia stimulates growth of oxyntic gland mucosa, but not ileum mucosa, the antiatrophy effect of
TCDD on mucosa of the oxyntic gland might in part be due to hypergastrinemia. In support of this interpretation,
TCDD treatment exerted an antiatrophy effect on the oxyntic gland mucosa only when
TCDD-treated animals were hypergastrinemic. For example, hypergastrinemia does not develop within the first 48 hr after
TCDD administration, and
TCDD treatment affords no protection against fasting-induced
atrophy of the oxyntic gland mucosa during this time. On the other hand, the ability of
TCDD treatment to protect against feed restriction-induced erosions of the oxyntic gland mucosa might be mediated by hypergastrinemia since these events occur at a later time.(ABSTRACT TRUNCATED AT 250 WORDS)