Eggens I, Bäckman L, Jakobsson A, Valtersson C
Division of Cellular and Neuropathology, Huddinge Hospital, Karolinska Institute, Sweden.
Br J Exp Pathol. 1988 Oct;69(5):671-83.
The lipid compositions of homogenates and microsomal fractions derived from surgical samples of highly differentiated human hepatoma, morphologically normal regions outside the tumours and from normal livers were analysed. A few enzyme activities were also assayed. Hepatoma microsomes demonstrated considerably lowered levels of cytochromes P-450 and b5. Hepatoma homogenates exhibited increased levels of cholesterol, normal amounts of dolichyl-P and slightly lowered levels of total phospholipid. The levels of dolichol, dolichol ester and ubiquinone in hepatoma homogenates were prominently decreased. In tumour microsomes the levels of cholesterol and dolichyl phosphate were increased considerably while the levels of phospholipid and dolichol were lowered. The phospholipid composition of tumour homogenates was roughly similar to that of control tissue. In tumour microsomes the relative amounts of phosphatidylserine and phosphatidylinositol were about 30% decreased, whereas the major phospholipids showed minor increases in amount. The rate and pattern of incorporation of [3H]glycerol into individual phospholipids in liver slices from control and hepatoma tissue did not differ to any larger extent. The fatty acid composition of tumour homogenates exhibited minor differences in comparison to the control with the greatest changes in the sphingomyelin fraction. In hepatoma microsomes the fatty acid compositions of the major phospholipids were altered moderately, with evident decreases in the relative amounts of the long-chain polyunsaturated fatty acids. In hepatoma homogenates the fatty acid composition of dolichol esters differed only slightly from the control pattern. These results indicate that the major disturbance in the lipid metabolism of highly differentiated hepatomas is localized to the mevalonate pathway, thus affecting mainly the levels of cholesterol, dolichol and ubiquinone.
对来自高分化人肝癌手术样本、肿瘤外形态正常区域以及正常肝脏的匀浆和微粒体组分的脂质组成进行了分析。还测定了一些酶活性。肝癌微粒体显示细胞色素P - 450和b5水平显著降低。肝癌匀浆中胆固醇水平升高，多萜醇磷酸酯含量正常，总磷脂水平略有降低。肝癌匀浆中多萜醇、多萜醇酯和泛醌的水平显著下降。肿瘤微粒体中胆固醇和磷酸多萜醇水平大幅升高，而磷脂和多萜醇水平降低。肿瘤匀浆的磷脂组成与对照组织大致相似。在肿瘤微粒体中，磷脂酰丝氨酸和磷脂酰肌醇的相对含量约降低30%，而主要磷脂的含量略有增加。[3H]甘油掺入对照和肝癌组织肝切片中各磷脂的速率和模式没有太大差异。与对照相比，肿瘤匀浆的脂肪酸组成有微小差异，鞘磷脂部分变化最大。在肝癌微粒体中，主要磷脂的脂肪酸组成有适度改变，长链多不饱和脂肪酸的相对含量明显降低。在肝癌匀浆中，多萜醇酯的脂肪酸组成与对照模式仅略有不同。这些结果表明，高分化肝癌脂质代谢的主要紊乱定位于甲羟戊酸途径，从而主要影响胆固醇、多萜醇和泛醌的水平。
