单次腹腔注射N-亚硝基甲基脲对年轻和成年雌性小鼠的年龄和剂量依赖性致癌作用。

Age and dose-dependent carcinogenic effects of N-nitrosomethylurea administered intraperitoneally in a single dose to young and adult female mice.

作者信息

Anisimov V N

机构信息

Laboratory of Experimental Tumours, N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia.

出版信息

J Cancer Res Clin Oncol. 1993;119(11):657-64. doi: 10.1007/BF01215984.

DOI:10.1007/BF01215984

PMID:8349723

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12201413/

Abstract

Female Swiss-derived SHR mice aged 3 ("young") and 12 months ("adult") were exposed to a single i.p. administration of N-nitrosomethylurea (NMU) at one of four doses: 0, 10, 20, or 50 mg/kg. The mean survival time of the young mice so treated was 440, 325, 398 and 182 days, and of the adult mice 221, 249, 191, and 168 days respectively. The incidence of all kinds of tumours in young mice was 40%, 64%, 77%, and 40%, of malignant tumours 33%, 43%, 57% and 20% of lung adenomas 7%, 14%, 40%, and 20% and of papillomas of the forestomach 0%, 14%, 23%, and 3% respectively. In adult mice these figures were for all kinds of tumours 52%, 52%, 56%, and 50%, for malignant tumours 44%, 52%, 52%, and 40%, for lung adenomas 7%, 0%, 8%, and 20%, for papillomas of the forestomach 0%, 0%, 12%, and 0% respectively. The exposure of adult female mice to various doses of NMU did not significantly increase the incidence of tumours or of malignant tumour incidence in comparison to age-matched controls. At the same time the latency of fatal tumours was shorter in the adult groups than in the young groups. Histoautoradiography of tissues of intact young and adult mice showed that there are no statistically significant age-related differences in the labelling index of forestomach epithelium, endometrium and lung alveolar wall epithelium. Only the labelling index of hepatocytes was decreased in the liver of adult mice in comparison to young ones. Comparison of the present experimental results with the data available on DNA synthesis and on O6-methylguanine repair in target tissues suggests a requirement for individual monitoring of age-related changes of biomarkers in exposure to carcinogenic agents. The analysis of data on the dose dependence of the carcinogenic effect of NMU against the background of a multistage model suggests an age-related accumulation of stochastically damaged cells for some tissues.

摘要

3月龄（“年轻”）和12月龄（“成年”）的瑞士来源雌性SHR小鼠接受腹腔注射一次N-亚硝基甲基脲（NMU），剂量为以下四种之一：0、10、20或50mg/kg。如此处理的年轻小鼠的平均存活时间分别为440、325、398和182天，成年小鼠的平均存活时间分别为221、249、191和168天。年轻小鼠各类肿瘤的发生率分别为40%、64%、77%和40%，恶性肿瘤的发生率分别为33%、43%、57%和20%，肺腺瘤的发生率分别为7%、14%、40%和20%，前胃乳头状瘤的发生率分别为0%、14%、23%和3%。成年小鼠中，这些数字分别为各类肿瘤52%、52%、56%和50%，恶性肿瘤44%、52%、52%和40%，肺腺瘤7%、0%、8%和20%，前胃乳头状瘤0%、0%、12%和0%。与年龄匹配的对照组相比，成年雌性小鼠暴露于不同剂量的NMU并未显著增加肿瘤发生率或恶性肿瘤发生率。同时，成年组致命肿瘤的潜伏期比年轻组短。对完整的年轻和成年小鼠组织进行组织放射自显影显示，前胃上皮、子宫内膜和肺泡壁上皮的标记指数在统计学上没有显著的年龄相关差异。与年轻小鼠相比，成年小鼠肝脏中仅肝细胞的标记指数降低。将目前的实验结果与靶组织中DNA合成和O6-甲基鸟嘌呤修复的现有数据进行比较表明，在接触致癌剂时需要对生物标志物的年龄相关变化进行个体监测。在多阶段模型背景下对NMU致癌作用的剂量依赖性数据进行分析表明，某些组织中存在与年龄相关的随机损伤细胞积累。