Castro G D, Delgado de Layño A M, Costantini M H, Castro J A
Centro de Investigaciones Toxicológicas (CEITOX)-CITEFA/CONICET, J.B. de La Salle 4397, 1603 Villa Martelli, Buenos Aires, Argentina.
Toxicology. 2001 Mar 7;160(1-3):11-8. doi: 10.1016/s0300-483x(00)00433-9.
Epidemiological evidence links alcohol intake with increased risk in breast cancer. Not all the characteristics of the correlation can be explained in terms of changes in hormonal factors. In this work, we explore the possibility that alcohol were activated to acetaldehyde and free radicals in situ by xanthine dehydrogenase (XDh) and xanthine oxidase (XO) and/or aldehyde oxidase (AO). Incubation of cytosolic fraction with xanthine oxidoreductase (XDh+XO) (XOR) cosubstrates (e.g. NAD+, hypoxanthine, xanthine, caffeine, theobromine, theophylline or 1,7-dimethylxanthine) significantly enhanced the biotransformation of ethanol to acetaldehyde. The process was inhibited by allopurinol and not by pyrazole or benzoate or desferrioxamine and was not accompanied by detectable formation of 1HEt. However, hydroxylated aromatic derivatives of PBN were detected, suggesting either that hydroxyl free radicals might be formed or that XOR might catalyze aromatic hydroxylation of PBN. No bioactivation of ethanol to acetaldehyde was detectable when a cosubstrate of AO such as N-methylnicotinamide was included in cytosolic incubation mixtures. Results suggest that bioactivation of ethanol in situ to a carcinogen, such as acetaldehyde, and potentially to free radicals, might be involved in alcohol breast cancer induction. This might be the case, particularly also in cases of a high consumption of purine-rich food (e.g. meat) or beverages or soft drinks containing caffeine.
流行病学证据表明，饮酒会增加患乳腺癌的风险。并非所有这种相关性的特征都可以用激素因素的变化来解释。在这项研究中，我们探讨了乙醇通过黄嘌呤脱氢酶（XDh）、黄嘌呤氧化酶（XO）和/或醛氧化酶（AO）在原位被激活生成乙醛和自由基的可能性。将胞质部分与黄嘌呤氧化还原酶（XDh+XO）（XOR）的共底物（如NAD+、次黄嘌呤、黄嘌呤、咖啡因、可可碱、茶碱或1,7-二甲基黄嘌呤）一起孵育，可显著增强乙醇向乙醛的生物转化。该过程被别嘌呤醇抑制，而不被吡唑、苯甲酸盐或去铁胺抑制，且未检测到1HEt的形成。然而，检测到了PBN的羟基化芳香衍生物，这表明可能形成了羟基自由基，或者XOR可能催化了PBN的芳香羟基化。当在胞质孵育混合物中加入AO的共底物（如N-甲基烟酰胺）时，未检测到乙醇向乙醛的生物激活。结果表明，乙醇在原位被生物激活为致癌物（如乙醛）并可能激活为自由基，这可能与酒精性乳腺癌的诱发有关。尤其是在大量食用富含嘌呤的食物（如肉类）或含咖啡因的饮料或软饮料的情况下，可能更是如此。
