Uchida K, Kado S, Onoue M, Tohyama K
Yakult Central Institute for Microbiological Research, Kunitachi.
Jpn J Cancer Res. 1997 Sep;88(9):807-14. doi: 10.1111/j.1349-7006.1997.tb00455.x.
Aberrant crypt foci (ACF) induced in the distal colon of F344 male rats, 4, 8, 12 and 35 weeks after the first administration of 1, 2-dimethylhydrazine-2HCl (DMH) were examined to determine whether a correlation exists between the nature of goblet cell mucin and the number of crypts (crypt multiplicity) comprising the ACF. According to the ACF score calculated from the results of the qualitative observation of sulfomucins (SuMs) and sialomucins (SiMs), the ACF in the 4th week showed a weak correlation between the nature of the mucus and crypt multiplicity, and the ACF of each class showed similar mucous profiles. From the 8th week, a significant difference (P < 0.01) was recognized between the ACF consisting of 3 crypts or less and those consisting of 4 crypts or more. The proportion of crypts with SiM predominance showed a decrease in the 8th week in the ACF consisting of 1 crypt and in the 12th week in the ACF consisting of 2 or 3 crypts, implying a recovery tendency. The ACF consisting of more than 4 crypts showed little change over time, retaining the tendency of SiM predominance. Ulex europaeus agglutinin-I (UEA-I) lectin-positive crypts appeared in the ACF. This finding was significantly more prominent (P < 0.001) in the ACF with SiM predominance than in the ACF with SuM predominance at each experimental period, and in the 12th week after the first administration of DMH, the incidence of ACF with UEA-I-reactive mucin was decreased in the ACF groups consisting of 3 crypts or less, compared with the ACF groups consisting of 4 or more crypts. These results suggest that the biological quality of mucus in ACF consisting of 4 or more crypts is different from that in ACF consisting of 3 crypts or less. This difference should be considered when ACF are used as an intermediate biomarker of colon cancer.
在首次给予1,2 - 二甲基肼 - 2HCl(DMH)后4、8、12和35周,对F344雄性大鼠远端结肠中诱导产生的异常隐窝灶(ACF)进行检查,以确定杯状细胞粘蛋白的性质与构成ACF的隐窝数量(隐窝多倍性)之间是否存在相关性。根据从硫粘蛋白(SuMs)和涎粘蛋白(SiMs)定性观察结果计算出的ACF评分,第4周的ACF在粘液性质与隐窝多倍性之间显示出弱相关性,并且每个类别的ACF显示出相似的粘液谱。从第8周开始,由3个或更少隐窝组成的ACF与由4个或更多隐窝组成的ACF之间存在显著差异(P < 0.01)。在由1个隐窝组成的ACF中,第8周以及在由2个或3个隐窝组成的ACF中,第12周时,以SiM为主的隐窝比例呈现下降趋势,这意味着有恢复的倾向。由4个以上隐窝组成的ACF随时间变化不大,保持着以SiM为主的趋势。荆豆凝集素 - I(UEA - I)凝集素阳性隐窝出现在ACF中。在每个实验时期,这一发现在以SiM为主的ACF中比在以SuM为主的ACF中显著更突出(P < 0.001),并且在首次给予DMH后的第12周,与由4个或更多隐窝组成的ACF组相比,由3个或更少隐窝组成的ACF组中具有UEA - I反应性粘蛋白的ACF发生率降低。这些结果表明,由4个或更多隐窝组成的ACF中粘液的生物学性质与由3个或更少隐窝组成的ACF中粘液的生物学性质不同。当将ACF用作结肠癌的中间生物标志物时,应考虑这种差异。