Effect of the β-diketones diferuloylmethane (curcumin) and dibenzoylmethane on rat mammary DNA adducts and tumors induced by 7,12-dimethylbenz[a]anthracene
Effect of the β-diketones diferuloylmethane (curcumin) and dibenzoylmethane on rat mammary DNA adducts and tumors induced by 7,12-dimethylbenz[a]anthracene
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DOI：
10.1093/carcin/19.6.1039
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发表时间：
1998-06-01
期刊：
影响因子：
4.7
通讯作者：
Wallig, M
中科院分区：
文献类型：
--
作者：
Singletary, K;MacDonald, C;Wallig, M
姜黄素是香料姜黄中的一种β-二酮成分，在几种动物模型中具有抗癌作用。本研究旨在寻找结构上与姜黄素相关的β-二酮类化合物，作为7，12-二甲基苯并[a]菲(DMBA)诱发大鼠乳腺癌变起始阶段的有效膳食阻断剂。在初步筛选出的在野生型Hepa1c1c7细胞和突变亚克隆中诱导苯醌还原酶(QR)活性的β-二酮化合物中，姜黄素(二阿魏酰甲烷)和二苯甲酰甲烷最有效。然而，当添加到雌性大鼠半纯饲料中时，二苯甲酰甲烷(1%)，而不是姜黄素(1%)，能有效地抑制体内乳腺DMBA-DNA加合物的形成。这种抑制乳腺加合物形成的作用与肝脏谷胱甘肽S转移酶活性、QR活性和7-乙氧基间苯二酚-O-脱乙基酶活性显著升高有关。雌性大鼠在给DMBA前14天饲喂添加0、1、0.5和1.0%二苯甲酰甲烷的饲料，与对照组相比，乳腺肿瘤的发生明显减少，而饲喂1.0%姜黄素饲料的大鼠，肿瘤的发生与对照组无显著差异。因此，二苯甲酰甲烷，以及其他可能与结构相关的β-二酮，需要作为乳腺癌化学预防阻滞剂进行检查。
Curcumin is a beta-diketone constituent of the spice turmeric that possesses anticarcinogenic properties in several animal models. The present studies were conducted in order to identify beta-diketones structurally-related to curcumin that would be effective dietary blocking agents toward the initiation stage of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Of the beta-diketone compounds initially screened for their capacity to induce quinone-reductase (QR) activity in wild-type Hepa1c1c7 cells and a mutant subclone, curcumin (diferuloylmethane) and dibenzoylmethane were most effective. However, when added to semipurified diets fed to female rats, dibenzoylmethane (1%), but not curcumin (1%), was effective in inhibiting in vivo mammary DMBA-DNA adduct formation. This inhibitory effect on mammary adduct formation was associated with a significant increase in liver activities of glutathione S-transferase, QR and 7-ethoxyresorufin-O-deethylase activities. Female rats provided diets supplemented with dibenzoylmethane at 0,1, 0.5 and 1.0% for 14 days prior to dosing with DMBA exhibited a significant decrease in mammary tumor development, compared with controls, However, tumor development for animals fed diets containing 1.0% curcumin was not different from that of controls. Therefore, dibenzoylmethane, and possibly other structurally-related beta-diketones, warrant examination as breast cancer chemopreventative blocking agents.