Alterations in intestinal uptake of putrescine and tissue polyamine concentrations in tumor-bearing rats.
Intestinal absorption of putrescine and tissue metabolism of polyamines were investigated in rats grafted with the rapidly growing Mat-Lylu prostatic tumor. These animals exhibited a dramatic 21% decrease in weight and protein, but not DNA, content of their intestinal mucosa, relative to healthy rats reared under similarly controlled nutritional conditions. No significant variation in the specific activities of intestinal 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 from cancerous or healthy rat intestine was a time dependent process at 25 degrees C. Equilibrium uptake was much greater than could be explained 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 saturable Michaelis-Menten carrier and passive diffusion. With respect to the kinetic parameters of putrescine transport, no significant changes were observed between the tumor-bearing and the control rats. After correction for nonspecific binding to the membranes, putrescine accumulation at equilibrium (75 min) was concentration-dependent and fit a single-site saturable model. Maximum accumulation of the diamine at equilibrium (Bmax) was increased by more than 46% in the cancerous rats relative to the controls, but the dissociation constant (Kd) was unchanged. Efflux of putrescine from the vesicles was slightly slower in the tumor-bearing group, but the differences were generally not significant. No change was observed with respect to the specific activity of ornithine decarboxylase and the concentration of polyamines in the intestinal mucosa. In Mat-Lylu grafted rats fed a standard diet supplemented with [14C]putrescine, about 19% of body radioactivity was recovered 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 healthy rats. Our findings indicate that the presence of the tumor evolves an adaptive response in the small intestine of the rat, involving an increased capacity of the brush-border membrane to accumulate putrescine.
Brachet
P
P
Unité de Nutrition Humaine et Physiologie Intestinale de l'I.N.R.A., Faculté de Pharmacie, Paris, France.
Quemener
V
V
Havouis
R
R
Tomé
D
D
Moulinoux
J P
JP
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005260:Female; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D007421:Intestine, Small / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011700:Putrescine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D014018:Tissue Distribution
D011700:Putrescine