Whitehead Tracy L, Holley Andy W, Korourian Soheila, Shaaf Saeid, Kieber-Emmons Thomas, Hakkak Reza
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Int J Mol Med. 2007 Oct;20(4):573-80.
Obesity increases mammary tumor development in Zucker rats following a single administration of the procarcinogen 7,12-dimenthylbenz(a)anthracene (DMBA). Fifty-day-old obese and lean female Zucker rats were orally gavaged with 65 mg/kg DMBA and sacrificed 139 days post DMBA treatment. At the end of the experiment, mammary tumors were detected in 68% of the obese rats compared to 32% of the lean group (P<0.001). 1H nuclear magnetic resonance (1H-NMR) spectra obtained for hydrophilic and lipophilic extracts from excised tumors illustrated fundamental differences in metabolic profiles between the two groups. Differences were observed for key choline compounds, namely phosphocholine and glycerophosphocholine, both markers of malignancy and apoptosis. In addition, levels of lactate, creatine, myo-inositol, alpha-glucose, alanine, leucine, glutamate, glutamine, tyrosine, phenylalanine, and NADH varied between the lean and obese groups. Principal component analysis indicated class separation between tumors from lean and obese rats based on their metabolic profiles, illustrating the potential for using 1H-NMR metabolomic methods for identifying altered metabolic pathways. Our results suggest that obesity enhances the risk for DMBA-induced mammary tumor development in rats. However, the mechanism for this increase in risk is currently unknown and will require further studies for elucidation.
在单次给予致癌物前体7,12 - 二甲基苯并(a)蒽（DMBA）后，肥胖会增加Zucker大鼠乳腺肿瘤的发生。50日龄的肥胖和瘦型雌性Zucker大鼠经口灌胃给予65 mg/kg DMBA，并在DMBA处理后139天处死。实验结束时，68%的肥胖大鼠检测到乳腺肿瘤，而瘦型组为32%（P<0.001）。从切除的肿瘤中获得的亲水性和脂溶性提取物的1H核磁共振（1H-NMR）光谱显示了两组之间代谢谱的根本差异。在关键胆碱化合物，即磷酸胆碱和甘油磷酸胆碱方面观察到差异，这两种化合物都是恶性肿瘤和细胞凋亡的标志物。此外，乳酸、肌酸、肌醇、α-葡萄糖、丙氨酸、亮氨酸、谷氨酸、谷氨酰胺、酪氨酸、苯丙氨酸和NADH的水平在瘦型和肥胖组之间有所不同。主成分分析表明，基于代谢谱，瘦型和肥胖大鼠的肿瘤之间存在类别区分，这表明使用1H-NMR代谢组学方法识别改变的代谢途径具有潜力。我们的数据表明，肥胖会增加大鼠中DMBA诱导的乳腺肿瘤发生风险。然而，这种风险增加的机制目前尚不清楚，需要进一步研究阐明。
