N-acetyltransferase expression and metabolic activation of the food-derived heterocyclic amines in the human mammary gland.
N-acetyltransferase expression and metabolic activation of the food-derived heterocyclic amines in the human mammary gland.
复制标题
人类乳腺中食物源性杂环胺的 N-乙酰转移酶表达和代谢激活。
作者：
N. Sadrieh;C. Davis;E. Snyderwine
在熟肉中发现的杂环胺（HCAs）是前致癌物，其通过N-乙酰基转移酶NAT 1和NAT 2的N-羟基化和O-乙酰化代谢活化。尽管代谢活化在HCA致癌性中的重要性以及发现几种HCA是啮齿动物乳腺致癌物，但对人类乳腺中的O-乙酰化活性一无所知。本研究检测了NAT在人乳腺中对N-羟基-HCAs 2-羟基氨基-1-甲基-6-苯基咪唑[4，5-B]吡啶（N-hydroxy-PhIP）和2-羟基-氨基-3-甲基咪唑[4，5-f]喹啉（N-hydroxy-IQ）的表达和催化活性。10名女性的乳腺胞浆和人乳腺上皮细胞原代培养物的裂解物通过NAT介导的O-乙酰转移酶代谢活化2-羟氨基-1-甲基-6-苯基咪唑[4，5-B]吡啶和2-羟氨基-3-甲基咪唑[4，5-f]喹啉，通过乙酰辅酶A增强的N-羟胺与小牛胸腺DNA的体外结合测定。N-乙酰化的对氨基水杨酸，一个特定的NAT 1的活动，但不是N-乙酰化的磺胺二甲嘧啶，一个特定的NAT 2的活动，在乳腺细胞质和人乳腺上皮细胞裂解物中检测到。人乳腺切片的免疫组织化学分析显示，在乳腺导管内衬上皮细胞中NAT 1蛋白染色阳性。逆转录-PCR分析表明，mRNA转录的NAT 1和NAT 2存在于人类乳腺，但没有NAT 2催化活性检测。我们的数据首次表明，人类乳腺对HCA食品诱变剂的代谢活化具有催化活性，并且这种活性最有可能是由乳腺导管上皮细胞中表达的NAT 1所贡献的。
The heterocyclic amines (HCAs) found in cooked meat are procarcinogens that are metabolically activated by N-hydroxylation followed by O-acetylation by the N-acetyltransferases NAT1 and NAT2. Despite the importance of metabolic activation in HCA carcinogenicity and the finding that several HCAs are rodent mammary gland carcinogens, nothing was known about O-acetylation activity in the human mammary gland. The current study examines the expression and catalytic activity of NAT toward the N-hydroxy-HCAs 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP) and 2-hydroxy-amino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ) in the human mammary gland. Mammary gland cytosol from 10 women and lysates from a primary culture of human mammary epithelial cells metabolically activated 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline by NAT-mediated 0-acetyltransferase, as measured by the acetyl CoA-enhanced binding of the N-hydroxylamines to calf thymus DNA in vitro. N-acetylation of p-aminosalicylic, an activity specific to NAT1, but not N-acetylation of sulfamethazine, an activity specific to NAT2, was detected in the mammary gland cytosols and human mammary epithelial cell lysates. Immunohistochemical analysis of human mammary gland sections showed positive staining for NAT1 protein in the epithelial cells lining the mammary gland ducts. Reverse transcription-PCR analysis showed that mRNA transcripts for both NAT1 and NAT2 were present in human mammary gland; however, no NAT2 catalytic activity was detectable. Our data demonstrate for the first time that the human mammary gland is catalytically active toward the metabolic activation of HCA food mutagens, and that this activity is most likely contributed by NAT1 expressed in the ductular epithelial cells of the mammary gland.
影响因子：
3.9
作者：
VATSIS, KP;WEBER, WW
通讯作者：
WEBER, WW