Lawson D, Paik W K, Morris H P, Weinhouse S
Cancer Res. 1977 Mar;37(3):850-6.
The rates of urea synthesis in rat liver and in a series of rat liver neoplasms with widely different growth rates and degree of differentiation were investigated using tissue slices incubated in a Krebs-Ringer bicarbonate buffer. Urea synthesis did not occur in fast-growing, poorly differentiated Novikoff and Morris 3924A hepatomas, but it did occur in slow-growing, well- and highly differentiated hepatomas; however, there was no correlation with growth rate or degree of differentiation. Urea synthesis was comparable with normal liver, at about 32 mumoles/hr/g tissue, in the slow-growing Morris hepatomas 21, 28A, 47C, and 44; but it was very low in two other slow-growing, highly differentiated hepatomas, 9618A and 20. The well-differentiated Morris hepatoma 5123C had intermediate levels of urea synthesis. This pattern of urea synthesis closely paralleled the previously reported activity of carbamyl phosphate synthetase in these tumors. The rate of urea synthesis was normal in livers of Buffalo rats bearing fast- or slow-growing hepatomas in low urea synthesis rates, but it was markedly lowered in the livers of rats bearing large, slow-growing tumors with high urea synthesis rates. Urea synthesis in liver declined as the tumors increased in size. The total rate of urea synthesis in liver and tumor, as well as the concentrations of urea in the serum and urine of tumor-bearing animals, remained remarkably constant throughout the period of tumor growth, suggesting the existence of a homeostatic mechanism that controls the urea cycle activity in accordance with the synthetic activity of the tumor. In parabiotic animals, carbamyl phosphate synthetase activity and urea synthesis were lowered in the host livers of partners bearing tumors with high carbamyl phosphate synthetase- and urea-synthetic activity, but there was no significant effect on urea cycle activity in the normal partners. This result discounts the likelihood of a circulating humoral factor that controls hepatic urea cycle activity.
使用在 Krebs-Ringer 碳酸氢盐缓冲液中孵育的组织切片，研究了大鼠肝脏以及一系列生长速率和分化程度差异很大的大鼠肝脏肿瘤中的尿素合成速率。快速生长、低分化的 Novikoff 和 Morris 3924A 肝癌中不发生尿素合成，但在生长缓慢、高分化和中分化的肝癌中会发生；然而，这与生长速率或分化程度无关。在生长缓慢的 Morris 肝癌 21、28A、47C 和 44 中，尿素合成与正常肝脏相当，约为 32 微摩尔/小时/克组织；但在另外两个生长缓慢、高分化的肝癌 9618A 和 20 中，尿素合成非常低。高分化的 Morris 肝癌 5123C 的尿素合成水平处于中等。这种尿素合成模式与先前报道的这些肿瘤中氨甲酰磷酸合成酶的活性密切平行。在尿素合成速率低的情况下，患有快速或缓慢生长肝癌的布法罗大鼠肝脏中的尿素合成速率正常，但在患有大的、生长缓慢且尿素合成速率高的肿瘤的大鼠肝脏中，尿素合成速率明显降低。随着肿瘤增大，肝脏中的尿素合成下降。在整个肿瘤生长期间，肝脏和肿瘤中尿素合成的总速率以及荷瘤动物血清和尿液中尿素的浓度保持相当恒定，这表明存在一种稳态机制，可根据肿瘤的合成活性来控制尿素循环活性。在联体动物中，在患有高氨甲酰磷酸合成酶和尿素合成活性肿瘤的伙伴的宿主肝脏中，氨甲酰磷酸合成酶活性和尿素合成降低，但对正常伙伴的尿素循环活性没有显著影响。这一结果排除了控制肝脏尿素循环活性的循环体液因子的可能性。
