探討紅花籽油攝取在促進荷爾蒙依賴型乳癌 之作用機制及影響乳癌生成之關鍵時期

Abstract

本論文主要是在探討，何生命期給予實驗動物自製紅花籽油飼料為促進乳癌生成的關鍵時刻，並探討脂肪酸、雌激素與乳癌生成間之可能作用機制。 利用DMBA(7,12-dimethylbenzanthracene)致癌劑來誘發SD雌性大鼠(Sprague-Dawley)乳腺癌，發現： （1） 乳癌潛伏期於給予DMBA後開始計算，在終生組、cox-2抑制劑組、魚油組、胚胎組、成年組中依序為︰49、63、63、70、91天； （2） 乳癌累積發生率則依序為︰51、43、33、69、44%；乳癌累積發生顆數依序為︰1.3、0.6、0.6、1.2、1.1顆。 （3） 每顆乳癌平均體積由大到小依序為︰胚胎組、cox-2抑制劑組、終生組、成年組、魚油組。 （4） 乳腺與乳癌組織中18:2ω6佔總脂肪酸之重量百分比，以胚胎組之比例較高。而各組乳癌組織中之20:4ω6佔總脂肪酸之重量百分比均較其乳腺組織高出近10倍之多。 （5） 比較懷孕時期餵給一般chow diet或實驗飼料，其血清中雌激素的濃度並無明顯差異，但於尿液中之雌激素代謝途徑Hydroxyestrogen和Methylestrogen的比例為懷孕時期餵給實驗飼料之母鼠較高，平均高出約2~4倍之多。 由實驗結果可印證本研究假說： (1) 親代懷孕時期攝取紅花籽油飼料最易促進其子代乳癌之生成。 (2) 飲食中18:2ω6的攝取可經由代謝轉換，增加乳腺組織之18:2ω6與 20:4ω6比例，且會改變雌激素代謝途徑，進而促進乳癌發生；魚油補 充或cox-2抑制劑的添加可減緩乳癌之生成。 本研究結果有助於了解促進乳癌生成之關鍵時期以及作用機制，進而致力於乳癌的預防與治療。

The aim of this study is to evaluate whether dietary safflower oil associated hormone dependent breast cancer originate in utero, and to understand the mechanism of dietary linoleic acid (18:2w6) on promoting breast cancer incidence, studied in DMBA (7, 12-dimethylbenzanthracene) induced Sprague-Dawley rat. Animal was fed with safflower oil experimental diet containing 8.8% of energy from 18:2w6 at a stage of utero, adult, whole life-span (WO), or the experimental diet supplemented with 1500ppm COX-2 inhibitor, celebrex (CE), or 0.1ml/day fish oil (FO). It was found that: (1) 50% animal vaginal opening at: utero (34-day-old), WO (39), adult (43). (2) Latency to the appearance of a breast cancer at first detection after DMBA administrated: WO (49-day-old), CE (63), FO (63), utero (70), adult (91). (3) % of cumulative breast cancer incidence after DMBA administrated: utero (69%), WO (51%), CE (43%), FO (33%), adult (44%). (4) Breast cancer multiplicity: WO (1.3), utero (1.3), adult (1.1), FO (0.6), CE (0.6). (5) Breast cancer volume (cm3): utero (6.8), CE (6.3), WO (2.5), adult (1.5), FO(1.0). (6) 20:4w6 level is 10 times more in tissue of mammary tumor than mammary gland. (7) The plasma estradiol level at day 18 pregnant animal feeding experimental diet or chow diet was no significant difference. (8) The ratio of 4-hydroxylestradiol to 4-methylestradiol is 2 times more in urine at day 18 pregnant animal feeding experimental diet than that feeding chow diet. We concluded that maternal dietary safflower oil in pregnancy is more potential in causing the breast cancer risk among female offspring than that dietary fed to pups through their whole life. We proposed that the breast cancer incidence was promoted by dietary 18:2w6 via increasing 20:4ω6 level in mammary gland.