Sørbye H, Kvinnsland S, Svanes K
Department of Surgery, University of Bergen, Haukeland Hospital, Norway.
Carcinogenesis. 1994 Apr;15(4):673-9. doi: 10.1093/carcin/15.4.673.
We have studied the effect of gastric exposure to 4.5 M NaCl on penetration of a carcinogen, N-[3H]methyl-N'-nitro-N-nitrosoguanidine (3H-MNNG) from the gastric lumen to proliferative cells in the gastric mucosa of Wistar rats at different time intervals after salt exposure. Cells in S-phase were labeled by incorporation of bromodeoxyuridine. Cells in S-phase labeled with 3H-MNNG (double-labeled cells) are the cell population at risk of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis. Ten minutes after salt damage the average percentage S-phase cells labeled with 3H-MNNG in pylorus was significantly decreased compared to control (1.2 +/- 0.6 and 9.5 +/- 0.7). Ten minutes after salt exposure a marked increase in gastric mucosal blood flow and leakage of fluid from the mucosa into the gastric lumen were observed, and the damaged gastric mucosa was covered by a thick mucoid layer. These factors may contribute to the reduced 3H-MNNG penetration into mucosa immediately after damage. Two hours after salt exposure the number of double-labeled cells (8.6 +/- 3.7/mm) and percentage S-phase cells labeled with 3H-MNNG (10.4 +/- 3.1) in pylorus did not differ from control (6.1 +/- 0.9/mm and 9.5 +/- 0.7). Twelve and 24 h after salt exposure the number of double-labeled cells (79.6 +/- 13.4/mm and 32.4 +/- 2.4/mm) and the percentage S-phase cells labeled with 3H-MNNG (29.7 +/- 2.8 and 18.9 +/- 1.3) in pylorus were significantly increased compared to control. Increased number of S-phase cells, a higher location of the proliferative zone in the glandular layer were observed 12-24 h after salt exposure and increased permeability of the mucosa to carcinogen was observed 12 h after salt exposure. These factors explain the increased number of double-labeled cells and the increased penetration of carcinogens to the proliferative cells, and may contribute to explain the previously described cocarcinogenic effect of salt on gastric carcinogenesis.
我们研究了胃暴露于4.5M氯化钠对致癌物N-[3H]甲基-N'-硝基-N-亚硝基胍（3H-MNNG）在盐暴露后不同时间间隔从胃腔渗透到Wistar大鼠胃黏膜增殖细胞的影响。通过掺入溴脱氧尿苷对S期细胞进行标记。用3H-MNNG标记的S期细胞（双标记细胞）是有N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导胃癌发生风险的细胞群体。盐损伤后十分钟，与对照组相比，幽门中用3H-MNNG标记的S期细胞平均百分比显著降低（分别为1.2±0.6和9.5±0.7）。盐暴露后十分钟，观察到胃黏膜血流量显著增加，且有液体从黏膜漏入胃腔，受损的胃黏膜被一层厚厚的黏液层覆盖。这些因素可能导致损伤后立即有较少的3H-MNNG渗透到黏膜中。盐暴露两小时后，幽门中双标记细胞数量（8.6±3.7/mm）和用3H-MNNG标记的S期细胞百分比（10.4±3.1）与对照组无差异（分别为6.1±0.9/mm和9.5±0.7）。盐暴露12小时和24小时后，幽门中双标记细胞数量（分别为79.6±13.4/mm和32.4±2.4/mm）以及用3H-MNNG标记的S期细胞百分比（分别为29.7±2.8和18.9±1.3）与对照组相比显著增加。盐暴露12 - 24小时后观察到S期细胞数量增加、增殖区在腺层中的位置更高，且盐暴露12小时后观察到黏膜对致癌物的通透性增加。这些因素解释了双标记细胞数量增加以及致癌物对增殖细胞的渗透增加，并可能有助于解释先前描述的盐对胃癌发生的促癌作用。
