Ethanol Metabolism and Melanoma.
Ethanol Metabolism and Melanoma.
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乙醇代谢和黑色素瘤。
作者：
乙醛（AcAH）是乙醇代谢的致癌副产物。乙醇相关的恶性肿瘤通常发生在乙醇摄入后暴露于AcAH的上胃肠道。出乎意料但却是真实的，流行病学证据支持饮酒与皮肤黑色素瘤之间的联系，表明皮肤暴露于乙醇和AcAH是皮肤癌的潜在原因。人类每天不可避免地以多种方式暴露于乙醇和AcAH，例如通过饮酒、食物摄入、吸入、皮肤接触和身体微生物群。这篇综述探讨了皮肤中乙醇和AcAH的来源，它们的代谢途径，以及乙醇和AcAH代谢酶功能失调的后果，重点是这些因素在黑色素瘤发生和进展中的作用。恶性黑色素瘤是最致命的皮肤癌。尽管在防晒教育方面做出了重大努力，但全球黑色素瘤发病率仍在上升，这引起了人们对黑色素瘤其他社会环境风险因素的关注。乙醇和乙醛（AcAH）在我们的饮食、药物、酒精饮料和环境中无处不在。在肝脏中，乙醇主要被氧化为AcAH，这是一种有毒的中间体，能够通过与蛋白质和DNA形成加合物来诱导肿瘤。一旦进入血液，乙醇和AcAH就能到达皮肤。虽然，像肝脏一样，皮肤具有代谢机制来解毒乙醇和AcAH，但当皮肤中的代谢酶功能失调时，乙醇/AcAH相关皮肤病的风险增加。这篇综述强调了皮肤乙醇代谢与黑色素瘤相关的证据。我们总结了皮肤乙醇和AcAH的各种来源，并描述了每种酒精代谢酶活性的降低如何影响对乙醇/AcAH毒性的敏感性阈值。来自Gene Expression Omnibus数据库的数据还显示，三种乙醇代谢酶（乙醇脱氢酶1B、P450 2E1和过氧化氢酶）和一种AcAH代谢酶（醛脱氢酶2）在黑色素瘤组织中显著降低。
Acetaldehyde (AcAH) is a carcinogenic byproduct of ethanol metabolism. Ethanol-associated malignancies commonly occur in the upper gastrointestinal tract exposed to AcAH after ethanol ingestion. Unexpectedly but true, emerging epidemiological evidence supports a link between alcohol consumption and cutaneous melanoma, suggesting skin exposure to ethanol and AcAH as potential causes of skin cancer. Humans are unavoidably exposed to ethanol and AcAH daily in multiple ways, such as through alcohol consumption, food ingestion, inhalation, skin contact, and bodily microbiota. This review examines the sources of ethanol and AcAH in the skin, their metabolic pathways, and the consequences of dysfunctional ethanol and AcAH metabolizing enzymes, focusing on the role of these factors in melanoma development and progression. Malignant melanoma is the deadliest form of skin cancer. Despite significant efforts in sun protection education, melanoma incidence is still rising globally, drawing attention to other socioenvironmental risk factors for melanoma. Ethanol and acetaldehyde (AcAH) are ubiquitous in our diets, medicines, alcoholic beverages, and the environment. In the liver, ethanol is primarily oxidized to AcAH, a toxic intermediate capable of inducing tumors by forming adducts with proteins and DNA. Once in the blood, ethanol and AcAH can reach the skin. Although, like the liver, the skin has metabolic mechanisms to detoxify ethanol and AcAH, the risk of ethanol/AcAH-associated skin diseases increases when the metabolic enzymes become dysfunctional in the skin. This review highlights the evidence linking cutaneous ethanol metabolism and melanoma. We summarize various sources of skin ethanol and AcAH and describe how the reduced activity of each alcohol metabolizing enzyme affects the sensitivity threshold to ethanol/AcAH toxicity. Data from the Gene Expression Omnibus database also show that three ethanol metabolizing enzymes (alcohol dehydrogenase 1B, P450 2E1, and catalase) and an AcAH metabolizing enzyme (aldehyde dehydrogenase 2) are significantly reduced in melanoma tissues.
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影响因子：
--
作者：
Batta, Nisha;Shangraw, Sarah;Nicklawsky, Andrew;Yamauchi, Takeshi;Zhai, Zili;Ravindran Menon, Dinoop;Gao, Dexiang;Dellavalle, Robert P;Fujita, Mayumi
通讯作者：
Fujita, Mayumi
影响因子：
64.8
作者：
Bertolotto, Corine;Lesueur, Fabienne;Bressac-de Paillerets, Brigitte
通讯作者：
Bressac-de Paillerets, Brigitte
影响因子：
11
作者：
Chang JS;Hsiao JR;Chen CH
通讯作者：
Chen CH
DOI：
10.1186/s13046-021-01926-6
发表时间：
2021-05-08
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
D'Aguanno S;Mallone F;Marenco M;Del Bufalo D;Moramarco A
通讯作者：
Moramarco A
影响因子：
4.5
作者：
Cheung, C;Davies, NG;Pease, CKS
通讯作者：
Pease, CKS