TUMOR-INCIDENCE IN A CHEMICAL CARCINOGENESIS STUDY OF NONHUMAN-PRIMATES
TUMOR-INCIDENCE IN A CHEMICAL CARCINOGENESIS STUDY OF NONHUMAN-PRIMATES
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DOI：
10.1006/rtph.1994.1013
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发表时间：
1994-04-01
影响因子：
3.4
通讯作者：
ADAMSON, RH
中科院分区：
文献类型：
--
作者：
THORGEIRSSON, UP;DALGARD, DW;ADAMSON, RH
本报告涵盖了一项为期32年的非人灵长类动物化学致癌研究，该研究由美国国家癌症研究所于1961年发起。373例种猴和正常对照的尸检记录显示，食蟹猴和恒河猴的自发性恶性肿瘤发生率很低（分别为1.5%和2.8%），而非洲绿色猴的发生率较高（8%）。大量的物质，包括各种食品添加剂、食品成分、环境污染物、N-亚硝基化合物、“经典"啮齿动物致癌物、致癌剂和免疫抑制剂，已被评估为长期致癌活性。经测试的食物成分中，可能与人体接触最相关的是人造甜味剂、环己基氨基磺酸盐和糖精。经过22年的连续给药，甜蜜素和糖精都没有显示出任何致癌作用的证据。同样，砷和滴滴涕的致癌潜力在给药15-22年后可以忽略不计。与此相反，真菌性食物污染物黄曲霉毒素B-1（AF B（1））和杂色曲霉素（SMT）被发现是强有力的肝致癌物。AFB还诱发胰腺腺癌、骨肉瘤和其他肿瘤。此外，苏铁蛋白的糖苷配基MAM醋酸盐诱导了多种肿瘤，但主要是肝细胞癌和肾细胞癌。最近引入殖民地的化合物包括熟肉中存在的三种杂环胺。这些化合物之一，2-氨基-3-甲基咪唑[4，5-f]喹啉（IQ）已被证明是猴子项目历史上最有效的肝癌原之一，在7年的暴露期内，在65%的动物中诱导恶性肝脏肿瘤。在所研究的经典啮齿动物致癌物中，氨基甲酸乙酯是唯一一种在猴子体内产生恶性肿瘤的致癌物。相反，除了两种N-亚硝基化合物外，所有N-亚硝基化合物都具有致癌性。二乙基亚硝胺（DENA）是食蟹猴、恒河猴和非洲绿色猴中最有效和可预测的肝癌原。然而，当腹腔注射给galagos（一种原猴）时，DENA主要诱导鼻腔粘液表皮样癌。N-甲基-N-亚硝基脲（MNU）是唯一持续产生消化道肿瘤的致癌物，主要是食管鳞状细胞癌。甲基苄肼（MIH）是唯一明确的致癌物，肿瘤发生率为33%，在大多数情况下引起急性非淋巴细胞白血病。(C)1994年出版社出版。
This report covers a 32-year period of an ongoing chemical carcinogenesis study in nonhuman primates, which was initiated by the National Cancer Institute in 1961. Autopsy records of 373 breeders and normal controls showed very law incidence of spontaneous malignant tumors in cynomolgus (1.5%) and rhesus (2.8%) monkeys, but considerably higher incidence in African green monkeys (8%). A large number of substances including a variety of food additives, food components, environmental contaminants, N-nitroso compounds, ''classical'' rodent carcinogens, antineoplastic agents, and immunosuppressive agents have been evaluated for long-term carcinogenic activity. Food components tested which are probably most relevant to human exposure are the artificial sweeteners, cyclamate and saccharin. After 22 years of continuous dosing, neither cyclamate nor saccharin have shown any evidence of carcinogenic effects. Similarly, the tumorigenic potential of arsenic and DDT was negligible after dosing for 15-22 years. In contrast, the fungal food contaminants, aflatoxin B-1 (AFB(1)) and sterigmatocystin (SMT), were found to be potent hepatocarcinogens. AFB, also induced adenocarcinomas of the pancreas, osteosarcomas, and other tumors. Also, the aglycone of cycasin, MAM acetate, induced a variety of tumors, but primarily hepatocellular and renal cell carcinomas. The compounds most recently introduced into the colony include three heterocyclic amines present in cooked meat. One of these compounds, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has proven to be one of the most potent hepatocarcinogens in the history of the monkey project, inducing malignant liver tumors in 65% of animals over a 7-year period of exposure. Of the classical rodent carcinogens studied, urethane was the only one which produced malignant tumors in the monkeys. Conversely, all except two of the N-nitroso compounds were carcinogenic. Diethylnitrosamine (DENA) was the most potent and predictable hepatocarcinogen in cynomolgus, rhesus, and African green monkeys. However, when administered intraperitoneally to galagos (a prosimian), DENA induced primarily mucoepidermoid carcinoma of the nasal cavity. N-Methyl-N-nitrosourea (MNU) was the only carcinogen persistently producing tumors in the digestive tract, mostly squamous cell carcinomas of the esophagus. Among the antineoplastic and immunosuppressive agents, procarbazine (MIH) was the only unequivocal carcinogen, with a 33% tumor incidence, causing acute nonlymphocytic leukemia in most of the cases. (C) 1994 Academic Press, Inc.