Préat V, Schulze C, Sterzel W, Eisenbrand G, Roberfroid M
Unité de Biochimie Toxicologique et Cancérologique, Université Catholique de Louvain, Brussels, Belgium.
IARC Sci Publ. 1987(84):200-1.
The capacities of nitrosamines to induce DNA single-strand breaks (SSB) and to initiate carcinogenesis in rat liver were compared. N-Nitrosodiethanolamine (NDELA), N-nitrosoethylhydroxyethylamine (NEHEA) and N-nitrosodiethylamine (NDEA) were equipotent in inducing DNA SSB when administered by gavage at doses of 0.35 mmol/kg, 0.015 mmol/kg and 0.37 mmol/kg, respectively. Male Wistar rats were injected with these nitrosamines and were then submitted to a selection procedure. Ten rats per group were sacrificed one week after the end of the selection to see the effects of the nitrosamines on the development of preneoplastic lesions. The numbers of gamma-glutamyl transferase (GGT)-positive lesions per cm2 were 0.8, 2.1, 5.2 and 40.1 in rats treated with saline, NDELA, NEHEA and NDEA, respectively. N-Nitrosobis(2,2,2-trifluorethyl)amine (6F-NDEA), a nongenotoxic and noncarcinogenic nitrosamine, induced 0.7 GGT-positive lesions per cm2. Ten rats per group also received 0.05% phenobarbital in their drinking-water and were killed six months after initiation in order to see the effect of the different nitrosamines on the incidence and yield of tumours. Two extrahepatic cancers were found after administration of NEHEA, whereas two hepatocellular carcinomas were detected after injection of NDEA. No cancer developed in the other groups. Although other factors may influence the process, these results indicate that no simple correlation can be established between induction of SSB in DNA and initiation of tumours by nitrosamines in rat liver.
比较了亚硝胺诱导大鼠肝脏DNA单链断裂（SSB）和引发致癌作用的能力。当分别以0.35 mmol/kg、0.015 mmol/kg和0.37 mmol/kg的剂量经口灌胃给予N-亚硝基二乙醇胺（NDELA）、N-亚硝基乙基羟乙胺（NEHEA）和N-亚硝基二乙胺（NDEA）时，它们诱导DNA SSB的能力相当。给雄性Wistar大鼠注射这些亚硝胺，然后进行筛选程序。每组10只大鼠在筛选结束后一周处死，以观察亚硝胺对癌前病变发展的影响。用生理盐水、NDELA、NEHEA和NDEA处理的大鼠每平方厘米γ-谷氨酰转移酶（GGT）阳性病变的数量分别为0.8、2.1、5.2和40.1。N-亚硝基双（2,2,2-三氟乙基）胺（6F-NDEA），一种非遗传毒性和非致癌性亚硝胺，每平方厘米诱导0.7个GGT阳性病变。每组10只大鼠在饮用水中还给予0.05%苯巴比妥，并在开始给药6个月后处死，以观察不同亚硝胺对肿瘤发生率和产量的影响。给予NEHEA后发现两例肝外癌，而注射NDEA后检测到两例肝细胞癌。其他组未发生癌症。尽管其他因素可能影响这一过程，但这些结果表明，在大鼠肝脏中，DNA中SSB的诱导与亚硝胺引发肿瘤之间无法建立简单的相关性。
