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大鼠腹侧前列腺中乙醇经黄嘌呤氧化酶生物活化生成乙醛和1-羟乙基自由基:分析其在大量饮酒促癌作用中的潜在作用。

Rat ventral prostate xanthine oxidase bioactivation of ethanol to acetaldehyde and 1-hydroxyethyl free radicals: analysis of its potential role in heavy alcohol drinking tumor-promoting effects.

作者信息

Castro G D, Delgado de Layño A M, Costantini M H, Castro J A

机构信息

Centro de Investigaciones Toxicológicas (CEITOX)-CITEFA/CONICET, J.B. de la Salle 4397, 1603 Villa Martelli, Buenos Aires, Argentina.

出版信息

Teratog Carcinog Mutagen. 2001;21(2):109-19.

Abstract

The ability of the ventral prostate cytosolic fractions to biotransform ethanol to acetaldehyde and 1-hydroxyethyl (1HEt) radicals was tested. Acetaldehyde formation was determined by GC-FID analysis in the head space of incubation mixtures. 1HEt was determined by spin trapping with PBN followed by extraction, silylation of the adduct and GC-MS of the product. Prostate cytosol was able to biotransform ethanol to acetaldehyde in the presence of NADH, hypoxanthine, xanthine, caffeine, theobromine, theophylline, and 1,7-dimethylxanthine but not in the presence of N-methylnicotinamide. All these biotransformations were inhibited by allopurinol and were sensitive to heating for 5 min at 100 degrees C. The biotransformation of ethanol to acetaldehyde in the presence of purines as cosubstrates was accompanied by the formation of hydroxyl and 1HEt radicals as detected by GC-MS, and the process was inhibited by allopurinol. Results suggest that prostate cytosolic xanthine oxidase is able to bioactivate ethanol to acetaldehyde and free radicals. The potential of these processes to be involved in tumor-promoting effects of heavy alcohol drinking in conjunction with high meat and/or purines consumption is analyzed. Multifactorial epidemiological studies considering that possibility might be convenient. Teratogenesis Carcinog. Mutagen. 21:109-119, 2001.

摘要

测试了腹侧前列腺胞质部分将乙醇生物转化为乙醛和1-羟乙基(1HEt)自由基的能力。通过气相色谱-火焰离子化检测(GC-FID)分析孵育混合物顶空中的乙醛形成情况。通过用PBN进行自旋捕集,随后进行萃取、加合物的硅烷化以及产物的气相色谱-质谱联用(GC-MS)来测定1HEt。在存在烟酰胺腺嘌呤二核苷酸(NADH)、次黄嘌呤、黄嘌呤、咖啡因、可可碱、茶碱和1,7-二甲基黄嘌呤的情况下,前列腺胞质能够将乙醇生物转化为乙醛,但在存在N-甲基烟酰胺的情况下则不能。所有这些生物转化均受到别嘌呤醇的抑制,并且对在100℃加热5分钟敏感。在嘌呤作为共底物存在的情况下,乙醇向乙醛的生物转化伴随着通过GC-MS检测到的羟基和1HEt自由基的形成,并且该过程受到别嘌呤醇的抑制。结果表明,前列腺胞质黄嘌呤氧化酶能够将乙醇生物活化成乙醛和自由基。分析了这些过程与大量饮酒以及高肉类和/或嘌呤摄入量共同作用参与肿瘤促进作用的可能性。考虑到这种可能性的多因素流行病学研究可能是合适的。致畸作用、致癌作用、致突变作用。2001年,21:109 - 119。

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