Mourelle M, Morris H P, Rubalcava B
Toxicology. 1980;15(3):173-80. doi: 10.1016/0300-483x(80)90051-7.
Adenylate cyclase activity was measured in plasma membranes isolated form Morris Hepatomas (44 and 47C) and from their host livers. We found that the enzyme activity in the tumours was very low, approx. 5% of the level in control and host livers. The amount of cAMP and cGMP in the tumours was also lower than in the host livers but the ratio of cGMP to cAMP in the tumours was increased by a factor of 4-5. The membrane binding capacities for the pancreatic hormones insulin and glucagon were measured. Hepatoma membranes bound less glucagon than those of livers. A decrease in the number of the glucagon receptors was found but there were no changes in the affinity constant. For insulin, we found the same binding capacity as the host and control livers; thus there was an increase in the ratio of insulin bound/glucagon bound in tumours as compared to controls. The plasma levels of insulin in the tumour bearing animals were approximately half of those in control, whereas the glucagon levels in plasma were 60-62% higher in tumour bearing animals. These results are discussed in terms of the characterization of normal, foetal and regenerating liver, in comparison with slow growing hepatomas. The levels of cAMP and cGMP are discussed with respect to control mechanisms of cell proliferation.
测定了从莫里斯肝癌(44型和47C型)及其宿主肝脏中分离出的质膜中的腺苷酸环化酶活性。我们发现肿瘤中的酶活性非常低,约为对照肝脏和宿主肝脏中水平的5%。肿瘤中cAMP和cGMP的含量也低于宿主肝脏,但肿瘤中cGMP与cAMP的比值增加了4至5倍。测定了质膜对胰腺激素胰岛素和胰高血糖素的结合能力。肝癌质膜结合的胰高血糖素比肝脏质膜少。发现胰高血糖素受体数量减少,但亲和常数没有变化。对于胰岛素,我们发现其结合能力与宿主和对照肝脏相同;因此,与对照相比,肿瘤中胰岛素结合/胰高血糖素结合的比值增加。荷瘤动物血浆中的胰岛素水平约为对照动物的一半,而荷瘤动物血浆中的胰高血糖素水平则高出60%至62%。结合正常肝脏、胎儿肝脏和再生肝脏的特征,与生长缓慢的肝癌进行比较,对这些结果进行了讨论。还就细胞增殖的控制机制讨论了cAMP和cGMP的水平。