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首页> 外文期刊>Mutation Research, C. Mutation Research Letters >DNA DAMAGING AND CELL PROLIFERATIVE ACTIVITY OF 1-METHYL-1-NITROSOUREA IN RAT GLANDULAR STOMACH MUCOSA
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DNA DAMAGING AND CELL PROLIFERATIVE ACTIVITY OF 1-METHYL-1-NITROSOUREA IN RAT GLANDULAR STOMACH MUCOSA

机译：大鼠腺体胃粘膜中1-甲基-1-硝基脲的DNA损伤和细胞增殖活性

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摘要

The DNA damaging and cell proliferative activity of 1-methyl-1-nitrosourea (MNU), a glandular stomach carcinogen, was studied in the pyloric mucosa of male F344 rats after administration by gastric tube. DNA damage was measured with unscheduled DNA synthesis (UDS) and DNA single strand scission as markers, while cell proliferation was measured with replicative DNA synthesis (RDS) and ornithine decarboxylase (ODC) as markers. MNU at doses of 30 and 60 mg/kg body wt and 80 min after administration dose-dependently induced UDS (49 and 79 (0 dose, 19) dpm/mu g DNA) measured by liquid scintillation counting in the presence of hydroxyurea (an inhibitor of RDS). RDS (DNA synthesis in the absence of hydroxyurea; 239 dpm/mu g DNA at 0 dose) did not increase at that time. MNU at doses of 10 and 60 mg/kg body wt and 2h after administration dose-dependently induced DNA single strand scission of 8.2 and 43.5 (0 dose, 1.4) elution rate constant (x10(-3)/ml). MNU at doses of 30 and 60 mg/kg body wt and 24h after administration dose-dependently induced an increase in RDS (1362 and 2393 (0 dose, 682) dpm/mu g DNA). MNU at doses of 60, 90 and 120 mg/kg body wt and 24h after administration dose-dependently induced an increase in ODC activity (22.0, 29.4 and 38.4 (0 dose, 6.3) p mol CO2/30 min/mg protein). These results suggest that MNU has possible tumor initiating activity (UDS and DNA single strand scission) and tumor promoting activity (RDS and ODC) in rat stomach mucosa.
机译：研究了雄性F344大鼠幽门粘膜经胃管给药后对腺胃癌致癌物1-甲基-1-亚硝基脲（MNU）的DNA损伤和细胞增殖活性。以计划外的DNA合成（UDS）和DNA单链断裂作为标记来测量DNA损伤，而以复制性DNA合成（RDS）和鸟氨酸脱羧酶（ODC）作为标记来测量细胞增殖。 MNU剂量为30和60 mg / kg体重，给药后80分钟，剂量依赖性诱导的UDS（49和79（0剂量，19）dpm /μgDNA）通过在羟基脲存在下进行液体闪烁计数来测量（ RDS抑制剂）。那时RDS（在不存在羟基脲的情况下进行DNA合成; 0剂量下239 dpm /μgDNA）没有增加。 MNU在10和60 mg / kg体重的剂量下以及给药后2h剂量依赖性诱导DNA单链断裂，洗脱速率常数为8.2和43.5（0剂量，1.4）（x10（-3）/ ml）。给药后30和60 mg / kg体重的MNU和24h的MNU剂量依赖性地引起RDS的增加（1362和2393（0剂量，682）dpm /μgDNA）。在给药后60、90和120 mg / kg体重和24h剂量下，MNU剂量依赖性地诱导ODC活性增加（22.0、29.4和38.4（0剂量，6.3）p mol CO2 / 30 min / mg蛋白）。这些结果表明，MNU在大鼠胃粘膜中可能具有肿瘤起始活性（UDS和DNA单链断裂）和肿瘤促进活性（RDS和ODC）。

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