Cascales C, Martin-Sanz P, Pittner R A, Hopewell R, Brindley D N, Cascales M
Biochem Pharmacol. 1986 Aug 15;35(16):2655-61. doi: 10.1016/0006-2952(86)90171-1.
Rats were injected daily for 8 weeks with 50 mg of thioacetamide per kg to produce liver tumours. Some of these rats were given three doses of 50 mg of an antitumoural Rh(III) complex/kg at 14, 9 and 5 days before the end of the thioacetamide treatment. Thioacetamide decreased the rate of weight gain of the rats and the Rh(III) complex partly restored it. The activities of ATP citrate lyase, acetyl-CoA carboxylase and fatty acid synthetase in the livers were decreased by thioacetamide treatment and the Rh(III) complex partly reversed this effect. By contrast the activity of malic enzyme was increased by both thioacetamide and the Rh(III) complex and this effect probably relates to NADPH production for detoxification rather than for lipogenesis. Treatment with thioacetamide increased the rate of synthesis of di- and triacylglycerols from glycerol phosphate by liver homogenates, the activity of phosphatidate phosphohydrolase and the incorporation of [3H]glycerol into liver triacylglycerol in vivo. The Rh(III) complex did not produce a significant reversal of these effects of thioacetamide on glycerolipid synthesis. The total uptake of intraportally injected [3H]glycerol by the livers of thioacetamide treated rats was decreased and this was associated with a lowered activity of glycerol kinase. Thioacetamide increased the activity of hepatic ornithine decarboxylase by about 40-fold, but the Rh(III) complex did not reverse this effect. However, the decrease in tyrosine aminotransferase activity that was produced by thioacetamide was partly reversed by the Rh(III) complex. These results are discussed in relation to the tumour-promoting effects of thioacetamide and the antitumoural action of the Rh(III) complex.
大鼠每天注射50毫克/千克硫代乙酰胺，持续8周以诱发肝肿瘤。在硫代乙酰胺治疗结束前14天、9天和5天，给其中一些大鼠注射三剂50毫克/千克的抗肿瘤铑（III）配合物。硫代乙酰胺降低了大鼠的体重增加速率，而铑（III）配合物部分恢复了该速率。硫代乙酰胺处理使肝脏中ATP柠檬酸裂解酶、乙酰辅酶A羧化酶和脂肪酸合成酶的活性降低，铑（III）配合物部分逆转了这种作用。相比之下，硫代乙酰胺和铑（III）配合物均增加了苹果酸酶的活性，这种作用可能与用于解毒而非脂肪生成的NADPH产生有关。硫代乙酰胺处理增加了肝匀浆从磷酸甘油合成二酰基甘油和三酰基甘油的速率、磷脂酸磷酸水解酶的活性以及[3H]甘油在体内掺入肝脏三酰基甘油的量。铑（III）配合物并未显著逆转硫代乙酰胺对甘油脂质合成的这些作用。硫代乙酰胺处理的大鼠肝脏对经门静脉注射的[3H]甘油的总摄取量降低，这与甘油激酶活性降低有关。硫代乙酰胺使肝脏鸟氨酸脱羧酶的活性增加约40倍，但铑（III）配合物并未逆转这种作用。然而，硫代乙酰胺导致的酪氨酸转氨酶活性降低被铑（III）配合物部分逆转。结合硫代乙酰胺的促肿瘤作用和铑（III）配合物的抗肿瘤作用对这些结果进行了讨论。
