ANTICARCINOGENS FROM FRIED GROUND-BEEF - HEAT-ALTERED DERIVATIVES OF LINOLEIC-ACID

ANTICARCINOGENS FROM FRIED GROUND-BEEF - HEAT-ALTERED DERIVATIVES OF LINOLEIC-ACID
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DOI:
10.1093/carcin/8.12.1881
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发表时间:
1987-12-01
期刊:
影响因子:
4.7
通讯作者:
PARIZA, MW
PARIZA, MW
中科院分区:
医学2区
文献类型:
--
作者:
HA, YL;GRIMM, NK;PARIZA, MW

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油炸碎牛肉含有抑制细菌诱变和 7,12-二甲基苯并[a]蒽 (DMBA) 引发小鼠表皮癌变的物质。抑制剂显然至少部分通过抑制细胞色素 P-450 活性起作用。通过 HPLC 分离出体外抑制细胞色素 P-450 活性的高度纯化级分,并通过 GC-MS 以及 UV 和质子 NMR 光谱进行表征。该级分含有四种亚油酸异构衍生物,每种衍生物含有共轭双键系统(称为 CLA)。在两阶段小鼠表皮癌变系统中测试了合成制备的 CLA(包含所有四种异构体)的抗起始活性。在应用DMBA前7天、3天和5分钟,分别以20、20和10mg的剂量应用CLA。对照小鼠用亚油酸或溶剂(丙酮)进行类似处理。开始后一周和此后每周两次,所有小鼠均用 12-O-tetrade-canoylphorbol-13-acetate 进行治疗,以促进肿瘤生长。亚油酸处理的小鼠和溶剂处理的对照小鼠之间的肿瘤发生率或产量没有差异。相比之下,与对照小鼠相比,接受 CLA 治疗的小鼠出现的乳头状瘤数量仅为对照小鼠的一半左右,并且肿瘤发生率较低。
Fried ground beef contains substances that inhibit mutagenesis in bacteria and the initiation of epidermal carcinogenesis in mice by 7,12-dimethylbenz[a]anthracene (DMBA). The inhibitors apparently act at least in part via inhibition of cytochrome P-450 activity. A highly purified fraction that inhibited cytochrome P-450 activityin vitrowas isolated by HPLC and characterized by GC—MS, and by UV and proton NMR spectroscopy. The fraction contained four isomeric derivatives of linoleic acid each containing a conjugated double-bond system (designated CLA). Synthetically prepared CLA (containing all four isomers) was tested for anti-initiation activity in the two-stage mouse epidermal carcinogenesis system. Seven days, 3 days and 5 min prior to DMBA application, CLA was applied at doses of 20, 20 and 10mg respectively. Control mice were treated similarly with linoleic acid or solvent (acetone). One week after initiation, and twice weekly thereafter, all mice were treated with 12-O-tetrade-canoylphorbol-13-acetate to effect tumor promotion. There was no difference in tumor incidence or yield between linoleic acid-treated mice and solvent-treated control mice. By contrast, the CLA-treated mice developed only about half as many papillomas and exhibited a lower tumor incidence compared with the control mice.