TUMOR-GROWTH RESULTS IN CHANGES IN PLACENTAL AMINO-ACID-TRANSPORT IN THE RAT - A TUMOR-NECROSIS-FACTOR ALPHA-MEDIATED EFFECT

The implantation of a fast growing tumour (Yoshida AH-130 ascites hepa toma) to late pregnant rats resulted in no changes in fetal growth, th is possibly being associated with an important increase in the fetal u ptake of maternal-derived amino acids [Carbo, Lopez-Soriano and Argile s (1995) Endocrinology 136, 3579-3584]. The present investigation was undertaken to see whether the presence of the tumour induced changes i n placental transport systems. For alanine transport, although no chan ges in affinity (K-m) were observed, tumour growth resulted in a 192% increase in V-max. in the Na+-independent component. Kinetic analysis of the Na+-dependent component resulted in two clearly different compo nents: while the low-affinity and high-capacity component was unaffect ed by tumour growth, the high-affinity, low-capacity component of the tumour-bearing rats showed an important increase in V-max. (78%). With regard to leucine transport, tumour burden induced important increase s in the Na+-independent component, not only in K-m (262%) but also in V-max. (189%). Since elevated tumour necrosis factor-alpha (TNF) conc entrations have been reported in this kind of tumour model, we perform ed the same type of transport experiments in rats chronically treated with TNF, the results obtained showing great similarities with those o bserved with tumour growth. The V-max. of Na+-independent alanine tran sport was also increased by the cytokine (104%) while no changes were observed in affinity. TNF treatment also induced an increase in the V- max. (67%) of the Na+-dependent (high-affinity, low-capacity) componen t while no changes in affinity were observed. Concerning leucine kinet ics, TNF treatment, as in the case of tumour growth, also increased K- m (155%) and V-max. (72%) associated with Na+-independent transport. I nterestingly, treatment with the cytokine increased both the K-m (43%) and V-max. (64%) of the Na+-dependent component. The inhibition patte rns suggest the existence of more that one Na+-dependent transport for alanine although the majority of the amino acid is transported throug h the A system. The results presented suggest that, during gestation, the mother is able to adapt her placental amino acid transport systems to compensate for the nitrogen drainage associated with tumour growth and thus provide the fetus with enough amino acids to allow its norma l growth, and that TNF could be responsible for the triggering of this compensatory mechanism.