Appel M J, van Garderen-Hoetmer A, Woutersen R A
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Cancer Res. 1994 Apr 15;54(8):2113-20.
It has been suggested that linoleic acid (LA) is responsible for the promoting effect of dietary polyunsaturated fat on pancreatic carcinogenesis via an accelerated prostaglandin synthesis, caused by metabolism of LA-derived arachidonic acid in (pre)neoplastic tissue. The purpose of the present study was to investigate whether dietary LA is the cause of pancreatic tumor promotion by a high fat diet. Five groups of 30 azaserine-treated rats and 5 groups of 30 N-nitrosobis(2-oxopropyl)amine-treated hamsters were maintained for 6 months (rats) and 12 months (hamsters) on high fat (25 weight %) AIN diets containing 2, 4, 6, 10, or 15 weight % LA. The results indicated that the strongest enhancing effect on the growth of pancreatic (pre)neoplastic lesions in rats and hamsters was obtained with 4 and 2 weight % of dietary LA, respectively. At higher LA levels the tumor response seemed to decrease rather than increase. In both rats and hamsters the fatty acid profiles of blood plasma and pancreas showed an accurate reflection of the dietary fatty acid profiles: a proportional increase in LA levels was observed in plasma and pancreas with increasing dietary LA. In both species plasma and pancreatic AA levels remained constant, except for arachidonic acid levels in rat plasma, which significantly increased with increasing dietary LA levels. Fatty acid profiles in hamster pancreatic tumors did not differ from fatty acid profiles in nontumorous pancreatic tissue from hamsters fed the same diet. Prostaglandin (PG) E2, 6-keto-PGF1 alpha, PGF2 alpha, and thromboxane B2-concentrations in nontumorous pancreatic tissue were similar among the diet groups. Ductular adenocarcinomas from hamster pancreas showed significantly higher levels of 6-keto-PGF1 alpha, PGF2 alpha, and thromboxane B2, but not of PGE2 in comparison with nontumorous pancreas. It is concluded that the strongest pancreatic tumor promotion by dietary LA is 4 weight % in rats and 2 weight % or less in hamsters, and that PGs may be involved in the development of ductular adenocarcinomas induced in hamster pancreas by N-nitrosobis(2-oxopropyl)amine.
有人提出，亚油酸（LA）通过加速前列腺素合成，导致（癌前）肿瘤组织中源自LA的花生四烯酸代谢，从而对膳食多不饱和脂肪在胰腺癌发生过程中的促进作用负责。本研究的目的是调查膳食LA是否是高脂肪饮食促进胰腺肿瘤的原因。五组每组30只经氮杂丝氨酸处理的大鼠和五组每组30只经N-亚硝基双（2-氧代丙基）胺处理的仓鼠，分别在含有2%、4%、6%、10%或15% LA的高脂肪（25%重量）AIN饮食中饲养6个月（大鼠）和12个月（仓鼠）。结果表明，分别在大鼠和仓鼠中，膳食LA含量为4%重量和2%重量时，对胰腺（癌前）肿瘤病变生长的促进作用最强。在LA水平较高时，肿瘤反应似乎下降而非增加。在大鼠和仓鼠中，血浆和胰腺的脂肪酸谱都准确反映了膳食脂肪酸谱：随着膳食LA含量增加，血浆和胰腺中的LA水平呈比例增加。在这两个物种中，血浆和胰腺中的花生四烯酸（AA）水平保持恒定，但大鼠血浆中的花生四烯酸水平随膳食LA水平增加而显著升高。仓鼠胰腺肿瘤中的脂肪酸谱与喂食相同饮食的仓鼠非肿瘤胰腺组织中的脂肪酸谱没有差异。各饮食组中非肿瘤胰腺组织中的前列腺素（PG）E2、6-酮-PGF1α、PGF2α和血栓素B2浓度相似。与非肿瘤胰腺相比，仓鼠胰腺的导管腺癌中6-酮-PGF1α、PGF2α和血栓素B2水平显著更高，但PGE2水平无显著差异。得出的结论是，膳食LA促进胰腺肿瘤的最强作用在大鼠中为4%重量，在仓鼠中为2%重量或更低，并且PGs可能参与了N-亚硝基双（2-氧代丙基）胺诱导的仓鼠胰腺导管腺癌的发生。
