Rushmore T H, Ghazarian D M, Subrahmanyan V, Farber E, Ghoshal A K
Department of Pathology, University of Toronto, Ontario, Canada.
Cancer Res. 1987 Dec 15;47(24 Pt 1):6731-40.
Fischer-344 rats fed a choline-devoid diet show lipid peroxidation in the liver nuclei, beginning at 1 day, reaching a peak at 3 days, and subsequently declining by 35 days. Lipid peroxidation in the mitochondria was seen first at 3 days, increased to a maximum at 28 days, and decreased after 35 days to undetectable values at 49 days. Lipid peroxidation was found in both nuclear and mitochondrial fractions both before and after stripping of their outer membranes. No microsomal lipid peroxidation could be detected at any time up to 63 days. The animals fed the same diet supplemented with choline showed no lipid peroxidation in any liver fraction. Animals given CCl4 showed the expected lipid peroxidation in the microsomes but not in the nuclear fraction. The administration of the free radical trapping agent, N-tert-butyl-alpha-phenylnitrone, prevented completely or almost so, microsomal lipid peroxidation induced by CCl4 and nuclear lipid peroxidation in the animals fed the choline-devoid, low methionine diet. The genesis of free radicals in the livers of rats fed a choline-devoid diet is considered as a likely hypothesis for the observed lipid peroxidation. The lipid peroxidation in turn is considered to be closely related to the induction of liver cell death and to the production of alterations in DNA. The DNA alterations coupled with regenerative liver cell proliferation suggest an attractive hypothesis for the initiation of hepatocarcinogenesis in rats fed a choline-devoid diet.
喂食缺乏胆碱饮食的Fischer-344大鼠肝脏细胞核中出现脂质过氧化，从第1天开始，第3天达到峰值，随后在35天时下降。线粒体中的脂质过氧化在第3天首次出现，在第28天增加到最大值，35天后下降，在49天时降至无法检测的值。在剥离外膜之前和之后，在细胞核和线粒体组分中均发现脂质过氧化。直至63天，在任何时候均未检测到微粒体脂质过氧化。喂食补充胆碱的相同饮食的动物在任何肝脏组分中均未显示脂质过氧化。给予四氯化碳的动物在微粒体中显示出预期的脂质过氧化，但在细胞核组分中未显示。给予自由基捕获剂N-叔丁基-α-苯基硝酮可完全或几乎完全防止由四氯化碳诱导的微粒体脂质过氧化以及喂食缺乏胆碱、低蛋氨酸饮食的动物的细胞核脂质过氧化。喂食缺乏胆碱饮食的大鼠肝脏中自由基的产生被认为是观察到的脂质过氧化的一个可能假设。脂质过氧化反过来被认为与肝细胞死亡的诱导以及DNA改变的产生密切相关。DNA改变与再生肝细胞增殖相结合，为喂食缺乏胆碱饮食的大鼠肝癌发生的起始提出了一个有吸引力的假设。
