Ichihara Toshio, Yoshino Hiroko, Doi Yuko, Nabae Kyoko, Imai Norio, Hagiwara Akihiro, Tamano Seiko, Morita Osamu, Tamaki Yasushi, Suzuki Hiroyuki
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan.
Food Chem Toxicol. 2008 Jan;46(1):157-67. doi: 10.1016/j.fct.2007.07.009. Epub 2007 Jul 25.
The modifying potential of diacylglycerol (DAG) oil on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay. DAG oil is a cooking oil that contains >80% diglycerides, <20% triglycerides and <5% monoglycerides. Male 6-week-old F344 rats (20 in each group) were sequentially treated with five carcinogens for initiation in different organ target sites for 4 weeks (DMBDD treatment), and then administered DAG oil at dietary levels of 0% (control), 1.375%, 2.75% or 5.5% [triacylglycerol (TGs), with the same fatty acid composition as DAG oil were also added at dietary levels of 5.5%, 4.125%, 2.75% and 0%, respectively, to maintain the same lipid level], or 5.5% high linoleic acid TG (HLTG), 5.5% high oleic acid TG (HOTG), or 5.5% medium-chain TG (MCTG) (as reference substances, mostly consisting of triacylglycerols) admixed into AIN-93G semi-synthetic diet, for an additional 24 weeks. Controls received standard diet without any supplementation as non-treated control. All animals were killed at the end of week 28, and the major organs were carefully examined for preneoplastic and neoplastic lesions. No DAG oil treatment-related changes were noted in survival, general conditions, body weights, food consumption and organ weights. Upon quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci of the liver, DAG oil was not found to exert any effects. The incidence of colon adenomas was significantly increased in rats given 1.375% DAG oil, but not 2.75% and 5.5% DAG oil, when compared to the control (5.5% TG group) value. Furthermore, incidences and multiplicity of hyperplasias and adenomas and/or adenocarcinomas were comparable across all DAG oil-treated groups. In contrast, incidences of colon adenomas and/or adenocarcinomas were significantly increased in rats given 5.5% HOTG, and adenomas with MCTG, but not 5.5% HLTG, as compared to the 5.5% TG value. Preneoplastic and neoplastic lesions induced by DMBDD treatment in various organs other than the large intestine were comparable in all cases. Thus, the current results indicate that DAG oil may not exert modifying potential on tumor development, even in the colon because of the lack of dose-dependence. DAG oil was equivalent to HOTG (standard cocking oil composed of naturally occurring fatty acids), with regard to colon tumor development. Further dose-response study concerning HOTG may be needed to confirm whether the enhancing effect of large intestine carcinogenesis exert or not.
在一项中期多器官致癌生物测定中，研究了二酰基甘油（DAG）油对肿瘤发展的潜在影响。DAG油是一种食用油，其中二甘油酯含量>80%，甘油三酯含量<20%，单甘油酯含量<5%。将6周龄雄性F344大鼠（每组20只）依次用五种致癌物在不同器官靶位点进行启动处理4周（二甲基苯并蒽二醇处理），然后分别以0%（对照）、1.375%、2.75%或5.5%的膳食水平给予DAG油[同时分别以5.5%、4.125%、2.75%和0%的膳食水平添加与DAG油脂肪酸组成相同的三酰基甘油（TGs），以维持相同的脂质水平]，或5.5%的高亚油酸TG（HLTG）、5.5%的高油酸TG（HOTG）或5.5%的中链TG（MCTG）（作为参考物质，主要由三酰基甘油组成）混入AIN-93G半合成饲料中，再持续喂养24周。对照组接受不添加任何物质的标准饲料作为未处理对照。在第28周结束时处死所有动物，并仔细检查主要器官的癌前和肿瘤病变。未观察到与DAG油处理相关的生存、一般状况、体重、食物消耗和器官重量的变化。对肝脏中谷胱甘肽S-转移酶胎盘形式（GST-P）阳性灶进行定量分析时，未发现DAG油有任何影响。与对照组（5.5%TG组）相比，给予1.375%DAG油的大鼠结肠腺瘤发生率显著增加，但给予2.75%和5.5%DAG油的大鼠未出现这种情况。此外，在所有DAG油处理组中，增生、腺瘤和/或腺癌的发生率及多发性相当。相比之下，与5.5%TG组相比，给予5.5%HOTG的大鼠以及给予MCTG的大鼠结肠腺瘤和/或腺癌发生率显著增加，但给予5.5%HLTG的大鼠未出现这种情况。在大肠以外的其他各种器官中，由二甲基苯并蒽二醇处理诱导的癌前和肿瘤病变在所有情况下相当。因此，目前的结果表明，即使在结肠中，由于缺乏剂量依赖性，DAG油可能对肿瘤发展没有潜在影响。就结肠肿瘤发展而言，DAG油与HOTG（由天然存在的脂肪酸组成的标准烹饪油）相当。可能需要进一步进行关于HOTG的剂量反应研究，以确认其是否对大肠致癌有增强作用。
