NORMALIZATION OF TUMOR-INDUCED INCREASES IN HEPATIC AMINO-ACID-TRANSPORT AFTER SURGICAL RESECTION

Background The liver of the host with cancer requires increased amount s of amino acids to support the synthesis of glucose and key defense p roteins. To study the effect of the growing tumor on hepatic amino aci d uptake, the authors measured hepatic transport activity in tumor-bea ring rats and in rats at Various times after tumor resection. Methods Fischer-344 rats were implanted subcutaneously with methylcholanthrene -induced fibrosarcoma cells (MCA sarcoma). When the tumors reached 10% of body weight, hepatic amino acid transport activity was assayed or the animals underwent surgical removal of the tumor. In animals that u nderwent tumor excision, livers were removed at 1, 3, or 5 days post-r esection, and hepatic plasma membrane vesicles (HPMVs) were prepared. Nontumor-bearing pair-fed rats undergoing sham implantation or sham re section served as controls. System N (glutamine), System A (MeAIB), an d System y(+) (arginine) transport activity were assayed, which allowe d the authors to compare differences in tumor-induced rates of transpo rt and the influence of resection on transport activity. Results Syste m A transport activity was unaltered by tumor growth. In contrast, the presence of the growing tumor increased arginine and glutamine uptake by the liver. Hepatic glutamine transport remained elevated for 5 day s after tumor resection, although by postoperative day 5 there was a t rend toward normalization. In contrast, arginine transport remained in creased by twofold on postresection day 1 and had normalized by postop erative day 3. The enhanced arginine transport was a result of an incr ease in maximal transport velocity (V-max) rather than a change in car rier affinity. Conclusions Increases in hepatic amino acid transport n ormalize within several days of tumor resection, indicating a key role for the tumor in the induction of this response. The observation that hepatic glutamine transport activity remains augmented after tumor re section longer than any other transporter studied suggests a key role for this amino acid in overall hepatic nitrogen metabolism and may par tially explain the persistent glutamine depletion that is characterist ic of the tumor-bearing host.