DIET AND CARCINOGEN ALTER LUMINAL BUTYRATE CONCENTRATION AND INTRACELLULAR PH IN ISOLATED RAT COLONOCYTES

A 2 x 2 factorial experiment was conducted to examine the effects of t wo different dietary fibers and carcinogen treatment on colonic lumina l short-chain fatty acid (SCFA) concentrations and intracellular pH (p H(i)) in rats. Twenty-four male Sprague-Dawley rats were divided into four groups, injected with a carcinogen [azoxymethane (AOM)] or normal saline (Sal), and fed one of two diets differing only in the type of dietary fiber [cellulose (Cell) or pectin (Pect)]. After 38 weeks of c onsuming these diets, the rats were euthanized, luminal contents were collected for analysis of SCFA concentrations, and colonocytes were is olated from the proximal and distal colon for subsequent determination of pH(i). Changes in pH(i) after the addition of exogenous sodium but yrate to the culture medium were also tested. The highest concentratio ns of SCFAs were produced by the control rats (saline injected) consum ing the pectin diet. Luminal butyrate concentrations were reduced in t hree of four colonic segments ofcarcinogeizinjected groups [proximal a nd distal cellulose (Prox Cell and Dist Cell) and distal pectin (Dist Pect)] compared with saline controls. The pH(i) was consistently highe r in colonocytes isolated from carcinogen-injected rats (Prox Cell/AOM = 6.95 vs. Prox Cell/Sal = 6.65, Prox Pect/AOM = 6.75 vs. Prox Pect/S al = 6.65, Dist Cell/AOM = 6.94 vs. Dist Cell/AOM = 6.85, Dist Pect/AO M = 6.92 vs. Dist Pect/Sal = 6.79) than in cells from saline-injected rats. Furthermore, in the majority of rats, pH(i) was lower in the pro ximal than in the distal colon. Addition of butyrate to cultured colon ocytes consistently lowered pH(i), but the effect was more pronounced in the carcinogen-injected animals. These data identify changes that o ccur intraluminally and intracellularly in colons of rats injected wit h AOM and suggest that, during tumorigenesis, alterations in butyrate production and basic colonocyte physiology may play an important role in the process.