Demonstration of ethanol-induced protein adducts in oral leukoplakia (pre-cancer) and cancer
Demonstration of ethanol-induced protein adducts in oral leukoplakia (pre-cancer) and cancer
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DOI：
10.1111/j.1600-0714.2007.00605.x
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发表时间：
2008-03-01
影响因子：
3.3
通讯作者：
Niemela, Onni
中科院分区：
文献类型：
--
作者：
Warnakulasuriya, Saman;Parkkila, Seppo;Niemela, Onni
背景：过量的饮酒是胃肠道癌上层癌的常见原因。然而，酒精诱导的癌变的主要机制仍然很差。来自口腔活检从36名受试者（11名英国人，25个日本）报告的标本报告滥用酒精。所有患者均被诊断出患有口服前癌（白细胞，n = 7）或鳞状细胞癌（SCC; n = 29）。使用单特异性抗体进行AA，MDA和HNE加合物的自动免疫染色。分子：AA，MDA和HNE加合物的阳性染色在发育不良或恶性上皮细胞中观察到相对较丰富的加合物物种。日本患者的亚组具有比英国样本更高的AA和MDA水平，尽管不是HNE。当材料分为SCC或Leukoplakia的材料时，MDA加合物（而不是其他抗原）在前组中更为突出。在不同的加合物之间发现了显着的相关性（AA与MDA，r = 0.68，p <0.001； AA vs. HNE，r = 0.47，p <0.01和MDA vs. HNE，r = 0.59，p <0.001）。此外，在这些样品中发现了细胞色素P450 2E1染色，与AA和MDA加合物都相关。结论：数据表明，在口腔误用者的口服误用者和口服白细胞和癌症的口腔组织中形成了AA-和脂质过氧化衍生的加合物。这些发现还支持AA的致病作用和过度的氧化应激在癌变中。
BACKGROUND: Excessive alcohol consumption is a common cause for upper gastrointestinal tract cancers. However, the primary mechanisms of alcohol-induced carcinogenesis have remained poorly defined.METHOD: We examined the generation and subcellular distribution of protein adducts with acetaldehyde (AA), the first metabolite of ethanol, and end products of lipid peroxidation, malondialdehyde (MDA) and 4-hydroxynonenal (HNE), from oral biopsy specimens obtained from 36 subjects (11 British, 25 Japanese) reporting alcohol misuse. All patients had been diagnosed with oral pre-cancer (leukoplakia, n = 7) or squamous cell carcinoma (SCC; n = 29). Automated immunostaining for AA, MDA and HNE adducts was performed using monospecific antibodies.RESULTS: Positive staining for AA, MDA and HNE adducts was observed in the dysplastic or malignant epithelial cells, HNE being relatively the most abundant adduct species. The subgroup of Japanese patients had higher levels of AA and MDA, although not HNE, than the British sample. When the material was divided to those with SCC or leukoplakia, MDA adducts but not the other antigens were more prominent in the former group. Significant correlations were found between the different adducts (AA vs. MDA, r = 0.68, P < 0.001; AA vs. HNE, r = 0.47, P < 0.01 and MDA vs. HNE, r = 0.59, P < 0.001). In addition, cytochrome P450 2E1 staining was found in these samples, correlating with both AA and MDA adducts.CONCLUSION: The data indicates that AA- and lipid peroxidation-derived adducts are formed in oral tissues of alcohol misusers with oral leukoplakia and cancer. The findings also support a pathogenic role of AA and excessive oxidative stress in carcinogenesis.