ALTERATIONS IN INTESTINAL UPTAKE OF PUTRESCINE AND TISSUE POLYAMINE CONCENTRATIONS IN TUMOR-BEARING RATS

Intestinal absorption of putrescine and tissue metabolism of polyamine s were investigated in rats grafted with the rapidly growing Mat-Lylu prostatic tumor. These animals exhibited a dramatic 21% decrease in we ight and protein, but not DNA, content of their intestinal mucosa, rel ative to healthy rats reared under similarly controlled nutritional co nditions. No significant variation in the specific activities of intes tinal brush-border membrane enzymes was observed, however, suggesting a comparable differentiation state of intestinal cells exists in both groups. Putrescine uptake by brush-border membrane vesicles prepared f rom cancerous or healthy rat intestine was a time dependent process at 25 degrees C. Equilibrium uptake was much greater than could be expla ined by equilibration of the vesicle space with putrescine, indicating that the diamine was bound to membrane sites. Kinetics of putrescine uptake at 2 min revealed that the process involves two components, a s aturable Michaelis-Menten carrier and passive diffusion. With respect to the kinetic parameters of putrescine transport, no significant chan ges were observed between the tumor-bearing and the control rats. Afte r correction for nonspecific binding to the membranes, putrescine accu mulation at equilibrium (75 min) was concentration-dependent and fit a single-site saturable model. Maximum accumulation of the diamine at e quilibrium (B-max) was increased by more than 46% in the cancerous rat s relative to the controls, but the dissociation constant (K-d) was un changed. Efflux of putrescine from the vesicles was slightly slower in the tumor-bearing group, but the differences were generally not signi ficant. No change was observed with respect to the specific activity o f ornithine decarboxylase and the concentration of polyamines in the i ntestinal mucosa. In Mat-Lylu grafted rats fed a standard diet supplem ented with [C-14]putrescine, about 19% of body radioactivity was recov ered in the tumor within 24 h. This was concomitant with a decrease in the percentage of radioactivity retained in the intestinal, renal and hepatic tissues, relative to that retained in the same tissues of hea lthy rats. Our findings indicate that the presence of the tumor evolve s an adaptative response in the small intestine of the rat, involving an increased capacity of the brush-border membrane to accumulate putre scine.