Klarich DawnKylee S, Penprase Jerrold, Cintora Patricia, Medrano Octavio, Erwin Danielle, Brasser Susan M, Hong Mee Young
School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, USA.
Department of Psychology, San Diego State University, San Diego, CA, USA.
Alcohol. 2017 Jun;61:25-31. doi: 10.1016/j.alcohol.2017.02.179. Epub 2017 Apr 18.
Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some studies have reported that moderate alcohol consumption may not contribute additional risk for developing colorectal cancer while others suggest that moderate alcohol consumption provides a protective effect that reduces colorectal cancer risk. The purpose of this study was to determine the effects of moderate voluntary alcohol (20% ethanol) intake on alternate days for 3 months in outbred Wistar rats on risk factors associated with colorectal cancer development. Colonic gene expression of cyclooxygenase-2, RelA, 8-oxoguanine DNA glycosylase 1, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase M1, and aldehyde dehydrogenase 2 were determined. Blood alcohol content, liver function enzyme activities, and 8-oxo-deoxyguanosine DNA adducts were also assessed. Alcohol-treated rats were found to have significantly lower 8-oxo-deoxyguanosine levels in blood, a marker of DNA damage. Alanine aminotransferase and lactate dehydrogenase were both significantly lower in the alcohol group. Moderate alcohol significantly decreased cyclooxygenase-2 gene expression, an inflammatory marker associated with colorectal cancer risk. The alcohol group had significantly increased glutathione-S-transferase M1 expression, an antioxidant enzyme that helps detoxify carcinogens, such as acetaldehyde, and significantly increased aldehyde dehydrogenase 2 expression, which allows for greater acetaldehyde clearance. Increased expression of glutathione-S-transferase M1 and aldehyde dehydrogenase 2 likely contributed to reduce mucosal damage that is caused by acetaldehyde accumulation. These results indicate that moderate alcohol may reduce the risk for colorectal cancer development, which was evidenced by reduced inflammation activity and lower DNA damage after alcohol exposure.
过量饮酒是与结直肠癌相关的一个风险因素；然而，一些研究报告称，适度饮酒可能不会增加患结直肠癌的额外风险，而另一些研究则表明，适度饮酒具有降低结直肠癌风险的保护作用。本研究的目的是确定在远交系Wistar大鼠中，连续3个月隔天适度自愿摄入酒精（20%乙醇）对与结直肠癌发生相关的风险因素的影响。测定了结肠中环氧合酶-2、RelA、8-氧代鸟嘌呤DNA糖基化酶1、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、谷胱甘肽-S-转移酶M1和乙醛脱氢酶2的基因表达。还评估了血液酒精含量、肝功能酶活性和8-氧代脱氧鸟苷DNA加合物。发现酒精处理的大鼠血液中8-氧代脱氧鸟苷水平显著降低，这是DNA损伤的一个标志物。酒精组的丙氨酸转氨酶和乳酸脱氢酶均显著降低。适度饮酒显著降低了环氧合酶-2基因的表达，环氧合酶-2是一种与结直肠癌风险相关的炎症标志物。酒精组中有助于对乙醛等致癌物进行解毒的抗氧化酶谷胱甘肽-S-转移酶M1的表达显著增加，且乙醛脱氢酶2的表达也显著增加，这使得乙醛清除能力更强。谷胱甘肽-S-转移酶M1和乙醛脱氢酶2表达的增加可能有助于减少由乙醛积累引起的黏膜损伤。这些结果表明，适度饮酒可能会降低结直肠癌的发生风险，这在酒精暴露后炎症活性降低和DNA损伤减少中得到了证实。
