Hinrichsen L I, Floyd R A, Sudilovsky O
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
Carcinogenesis. 1990 Oct;11(10):1879-81. doi: 10.1093/carcin/11.10.1879.
The mechanism(s) by which a diet devoid of choline (CD) induces hepatocellular carcinomas in rats remains unknown. Although animals fed this diet develop nuclear lipid peroxidation, suggesting oxidative DNA damage, there is no direct evidence that this occurs. In this study, 8-hydroxydeoxyguanosine (8-OHdG), a DNA adduct generated by reactive oxygen species, was analyzed in the liver of rats fed a CD diet and in controls receiving a choline-sufficient (CS) diet. After partial hepatectomy, the animals were injected with diethylnitrosamine (DEN, 50 mg/kg body wt) or with saline and fed a CD or CS diet for 24 weeks. While liver DNA from rats injected either with DEN or saline and fed a CS diet did not show detectable amounts of the nucleotide, those who were fed DEN/CD and saline/CD demonstrated similar, easily measurable levels of 8-OHdG. These results indicate that there is a positive association between the continuous administration of a CD diet and the production of 8-OHdG in liver DNA, and support the idea that oxidative DNA damage is involved in carcinogenesis by a CD diet.
缺乏胆碱（CD）的饮食诱导大鼠肝细胞癌的机制尚不清楚。尽管喂食这种饮食的动物会发生核脂质过氧化，提示存在氧化性DNA损伤，但尚无直接证据表明确实如此。在本研究中，对喂食CD饮食的大鼠肝脏以及接受胆碱充足（CS）饮食的对照大鼠肝脏中的8-羟基脱氧鸟苷（8-OHdG，一种由活性氧产生的DNA加合物）进行了分析。部分肝切除术后，给动物注射二乙基亚硝胺（DEN，50 mg/kg体重）或生理盐水，并喂食CD或CS饮食24周。注射DEN或生理盐水并喂食CS饮食的大鼠肝脏DNA未检测到该核苷酸，而喂食DEN/CD和生理盐水/CD的大鼠肝脏DNA中8-OHdG水平相似且易于测量。这些结果表明，持续给予CD饮食与肝脏DNA中8-OHdG的产生呈正相关，并支持氧化性DNA损伤参与CD饮食致癌作用的观点。
