Yang C S, Chhabra S K, Hong J Y, Smith T J
Laboratory for Cancer Research, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
J Nutr. 2001 Mar;131(3s):1041S-5S. doi: 10.1093/jn/131.3.1041S.
Diallyl sulfide (DAS) is a flavor compound derived from garlic and is sequentially converted to diallyl sulfoxide (DASO) and diallyl sulfone (DASO(2)) by cytochrome P(450) 2E1 (CYP2E1). These compounds have been shown to reduce the incidence of a multitude of chemically induced tumors in animal models. The impediment of phase I activation of these carcinogens is hypothesized to be accountable for the reduction in tumor incidence. Indeed, DAS, DASO and DASO(2) are competitive inhibitors of CYP2E1. DASO(2), in addition, is a suicide inhibitor of CYP2E1. These compounds have been shown to reduce carbon tetrachloride-, N-nitrosodimethylamine- and acetaminophen-induced toxicity in rodents. All three chemicals are substrates for CYP2E1. The protective effect was observed when the organosulfur compounds were given before, during or soon after chemical treatment. DAS and DASO(2) inhibited the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and related lung tumorigenesis in A/J mice. Because CYP2E1 does not play a key role in NNK activation, the inhibition of other CYP enzymes active in NNK metabolism is likely. DAS also has been shown to induce other CYP and phase II enzymes as well as decrease hepatic catalase activity. All of these effects are observed at concentrations much higher than what is normally ingested by humans. The biological activities of garlic and its related compounds at lower concentrations that mimic human consumption remain to be studied further.
二烯丙基硫醚（DAS）是一种源自大蒜的风味化合物，通过细胞色素P450 2E1（CYP2E1）依次转化为二烯丙基亚砜（DASO）和二烯丙基砜（DASO₂）。这些化合物已被证明可降低动物模型中多种化学诱导肿瘤的发生率。据推测，这些致癌物的I相激活受阻是肿瘤发生率降低的原因。实际上，DAS、DASO和DASO₂是CYP2E1的竞争性抑制剂。此外，DASO₂还是CYP2E1的自杀性抑制剂。这些化合物已被证明可降低啮齿动物中四氯化碳、N-亚硝基二甲胺和对乙酰氨基酚诱导的毒性。这三种化学物质都是CYP2E1的底物。在化学处理前、处理期间或处理后不久给予有机硫化合物时，均观察到了保护作用。DAS和DASO₂抑制了4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮（NNK）的生物活化以及A/J小鼠中相关的肺癌发生。由于CYP2E1在NNK活化中不发挥关键作用，因此可能抑制了NNK代谢中其他活跃的CYP酶。DAS还被证明可诱导其他CYP和II相酶，并降低肝脏过氧化氢酶活性。所有这些作用都是在远高于人类正常摄入量的浓度下观察到的。大蒜及其相关化合物在模拟人类摄入量的较低浓度下的生物活性仍有待进一步研究。
