George R, Goldfarb S
Cancer Res. 1980 Dec;40(12):4717-21.
The effect of i.v. injection of mevalonate on the activity of microsomal 3-hydroxy-3-methylglutaryl Coenzyme A reductase was studied in livers from non-tumor-bearing rats and in host liver and hepatomas from rats bearing transplantable Morris hepatoma 7800. We confirmed that a single bolus injection of 100 mg of mevalonate in non-tumor-bearing male rats caused a 90% inhibition of hepatic 3-hydroxy-3-methylglutaryl Coenzyme A reductase activity within 2 hr. In two experiments mevalonate injection caused a 50 to 60% reduction in enzyme activity of hepatomas but no significant decline in the enzyme activity in host livers. Thirty in after injection of [14C]mevalonate in a similarly sized bolus, the ratio of specific activities of cholesterol in liver:hepatoma:kidney:blood was 13:5.6:0.5:1. Thus, both the liver and hepatoma efficiently utilized mevalonate for the synthesis of cholesterol. The precise cause of the inhibition of enzyme activity in the liver of non-tumor-bearing rats and in the transplantable hepatomas is not clear from this study. However, on the basis of other published reports, we suggest that it resulted from the accumulation of endogenous cholesterol in microsomal membrane. The activity of cholesterol 7 alpha-hydroxylase, the rate-controlling enzyme for bile acid synthesis, was also studied in the hepatoma, but, in general, it did not differ from that in the host liver or control liver.
研究了静脉注射甲羟戊酸对未患肿瘤大鼠肝脏以及移植了可移植性莫里斯肝癌7800的大鼠的宿主肝脏和肝癌中微粒体3-羟基-3-甲基戊二酰辅酶A还原酶活性的影响。我们证实，在未患肿瘤的雄性大鼠中单次推注100 mg甲羟戊酸会在2小时内导致肝脏3-羟基-3-甲基戊二酰辅酶A还原酶活性受到90%的抑制。在两项实验中，注射甲羟戊酸使肝癌的酶活性降低了50%至60%，但宿主肝脏中的酶活性没有显著下降。以类似大小的推注量注射[14C]甲羟戊酸30分钟后，肝脏：肝癌：肾脏：血液中胆固醇的比活性为13:5.6:0.5:1。因此，肝脏和肝癌都有效地利用甲羟戊酸来合成胆固醇。从这项研究中尚不清楚未患肿瘤大鼠肝脏和可移植肝癌中酶活性受到抑制的确切原因。然而，根据其他已发表的报告，我们认为这是由于微粒体膜中内源性胆固醇的积累所致。还研究了肝癌中胆汁酸合成的限速酶胆固醇7α-羟化酶的活性，但总体而言，它与宿主肝脏或对照肝脏中的活性没有差异。
