Sauer L A, Dauchy R T
Cancer Res. 1986 Feb;46(2):689-93.
These experiments were designed to determine the characteristics of lactic acid utilization and production in vivo in Jensen sarcoma and Morris hepatoma 7288CTC. Arteriovenous differences for lactic and pyruvic acids, glucose, and the ketone bodies were measured across "tissue-isolated" tumors growing in fed and fasted rats. Lactic acid was utilized (n = 18), produced (n = 24), or neither utilized nor produced (n = 1) by the tumors. Net tumor lactate production or utilization did not depend on the mean rate of glucose utilization which was the same in the lactate-utilizing and -producing tumors. For the lactic acid-utilizing tumors, the mean arterial whole blood lactate concentration entering the tumor was 3.47 +/- 0.39 mM, and the concentration in the tumor venous blood was 2.31 +/- 0.25 mM. For the lactic acid-producing tumors, the mean arterial lactic acid concentration was 1.29 +/- 0.10 mM, and the tumor venous blood concentration was 2.19 +/- 0.19 mM. Thus, both lactate-producing and lactate-utilizing tumors showed identical rates of glucose utilization and identical lactic acid concentrations in the venous blood leaving the tumors. Metabolite levels were also measured in tumors that were freeze clamped in situ immediately following collection of the arterial and tumor venous blood samples. The lactic acid content in the tumor mass (corrected for total tumor water) and the concentration in the tumor venous blood plasma were nearly identical, suggesting that the lactate concentrations in the tumor cells and tumor venous blood are at equilibrium. Transport of lactic acid between arterial plasma and tumor or between tumor and venous plasma was always down a concentration gradient; net lactate uptake and release in these tumors followed the law of mass action. High lactate concentrations were not observed in the Jensen sarcomas or in the venous blood leaving these tumors, and we were unable to confirm earlier studies indicating that Jensen sarcomas are consistently high net lactate producers in vivo.
这些实验旨在确定Jensen肉瘤和Morris肝癌7288CTC体内乳酸利用和生成的特征。在喂食和禁食大鼠体内生长的“组织隔离”肿瘤中,测量了乳酸、丙酮酸、葡萄糖和酮体的动静脉差值。肿瘤对乳酸的利用情况为:利用乳酸的有18例,产生乳酸的有24例,既不利用也不产生乳酸的有1例。肿瘤乳酸的净生成或利用并不取决于葡萄糖的平均利用速率,利用乳酸和产生乳酸的肿瘤中葡萄糖平均利用速率相同。对于利用乳酸的肿瘤,进入肿瘤的平均动脉全血乳酸浓度为3.47±0.39 mM,肿瘤静脉血中的浓度为2.31±0.25 mM。对于产生乳酸的肿瘤,平均动脉乳酸浓度为1.29±0.10 mM,肿瘤静脉血浓度为2.19±0.19 mM。因此,产生乳酸和利用乳酸的肿瘤在葡萄糖利用速率以及离开肿瘤的静脉血中乳酸浓度方面表现相同。在采集动脉血和肿瘤静脉血样本后立即原位冷冻钳夹的肿瘤中,也测量了代谢物水平。肿瘤组织中的乳酸含量(校正总肿瘤水分后)与肿瘤静脉血浆中的浓度几乎相同,这表明肿瘤细胞和肿瘤静脉血中的乳酸浓度处于平衡状态。乳酸在动脉血浆与肿瘤之间或肿瘤与静脉血浆之间的转运始终是顺着浓度梯度进行的;这些肿瘤中乳酸的净摄取和释放遵循质量作用定律。在Jensen肉瘤或离开这些肿瘤的静脉血中未观察到高乳酸浓度,我们无法证实早期研究表明Jensen肉瘤在体内始终是高净乳酸生产者这一结论。