Mak K M, Lieber C S
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, Bronx, New York 10468, USA.
Anat Rec. 2000 Aug 1;259(4):405-12. doi: 10.1002/1097-0185(20000801)259:4<405::AID-AR40>3.0.CO;2-K.
In the accompanying article, we established that in the rat distal colon expression of H, B, and Le(b) blood group antigens by goblet cells is phenotypically fetal in nature. Because of the cocarcinogenic property of ethanol, the present study examined the effects of dietary ethanol consumption, fasting, and withdrawal on the expression of these antigens in the adult rat colon. To that effect, male adult Sprague-Dawley rats were pair-fed ethanol-containing or control Lieber-DeCarli liquid diets for 3 weeks. The effects of ethanol withdrawal were studied in rats fed the ethanol-containing diet for 3 weeks followed by the control diet for 1, 3, and 6 days. In rats fed the control diet, no antigen expression in the distal colon was observed, as expected. Ethanol feeding for 3 weeks resulted in a striking reappearance of H, B, and Le(b) antigens in goblet cells of the distal colon. In colonic crypts, a lower-to-upper crypt gradient of increasing numbers of positive goblet cells was present, suggesting that the induction of antigen expression paralleled the differentiation of goblet cells. After an overnight fast, the number of positive cells was significantly decreased. Withdrawal of ethanol for 1 day further decreased the number of positive goblet cells. The decrease was reflected by a downward shift in the number of positive cells per crypt column, which was more striking in the lower and mid-crypt segments than in the upper segment, suggesting that antigen expression was more labile in immature differentiating goblet cells than in mature ones. No antigen staining of goblet cells was detected after 3 and 6 days of ethanol withdrawal. Hence, expression of H, B, and Le(b) antigens by goblet cells of the distal colon can be modulated by ethanol consumption. Expression in the distal colon of A and Le(a) antigens, which did not exhibit a fetal phenotype, was not affected by ethanol feeding. In conclusion, because of the oncofetal phenotype of H, B, and Le(b) antigens, their reappearance in the distal colon may serve as a cytochemical marker for early recognition of epithelial changes of the colon in ethanol-related cocarcinogenesis before more overt manifestations of neoplasia.
在随附的文章中,我们证实大鼠远端结肠中杯状细胞表达的H、B和Le(b)血型抗原在表型上具有胎儿期特征。由于乙醇具有促癌特性,本研究考察了成年大鼠结肠中饮食摄入乙醇、禁食及戒断对这些抗原表达的影响。为此,将成年雄性Sprague-Dawley大鼠成对喂养含乙醇或对照的Lieber-DeCarli液体饮食3周。对喂养含乙醇饮食3周后再分别喂养对照饮食1天、3天和6天的大鼠研究乙醇戒断的影响。如预期的那样,在喂养对照饮食的大鼠中,未观察到远端结肠有抗原表达。喂养乙醇3周导致远端结肠杯状细胞中H、B和Le(b)抗原显著重现。在结肠隐窝中,阳性杯状细胞数量从隐窝下部到上部呈递增梯度,这表明抗原表达的诱导与杯状细胞的分化平行。禁食过夜后,阳性细胞数量显著减少。戒断乙醇1天进一步减少了阳性杯状细胞的数量。这种减少表现为每个隐窝柱中阳性细胞数量的下移,在隐窝下部和中部比上部更明显,这表明在未成熟的分化杯状细胞中抗原表达比成熟杯状细胞更不稳定。戒断乙醇3天和6天后未检测到杯状细胞的抗原染色。因此,远端结肠杯状细胞中H、B和Le(b)抗原的表达可受乙醇摄入调节。未表现出胎儿期表型的A和Le(a)抗原在远端结肠的表达不受乙醇喂养影响。总之,由于H、B和Le(b)抗原具有肿瘤胎儿期表型,它们在远端结肠中的重现可能作为一种细胞化学标志物,用于在肿瘤形成更明显表现之前早期识别乙醇相关促癌过程中结肠上皮的变化。