Farrelly J G, Thomas B J, Lijinsky W
NCI-Frederick Cancer Research Facility, LBI-Basic Research Program, MD 21701.
IARC Sci Publ. 1987(84):87-90.
N-Nitrosodiethanolamine (NDELA) labelled with 14C at the alpha carbon was administered by gavage to adult male Fischer 344 rats at various doses ranging from 0.6 to 100 mg per rat. The proportion of the dose excreted as 14CO2 was small, ranging from 0.27% at the lowest dose to 0.83% at the highest in 24 h. At all doses, approximately 95% of the dose of radioactivity (most of which was NDELA) appeared in the urine within 24 h, but the proportion of metabolites increased from 7% to 14% from the lowest to the highest dose. The specific activity of the nucleic acids isolated from the liver of rats given 100 mg and 100 microCi of NDELA was very low and was the same at 6 h and 24 h after treatment (70 dpm/mg DNA, 92-95 dpm/mg RNA). N7-(2-Hydroxyethyl)guanine and O6-(2-hydroxyethyl)-guanine were tentatively identified in the hydrolysates of the nucleic acids, comprising 10% and 4%, respectively, of the DNA radioactivity; there was no difference between the amounts found 6 h and 24 h after NDELA treatment. In addition to NDELA, four components were separated from rat urine, and two were identified. One is the glucuronide of NDELA, the other is N-nitroso-N-(2-hydroxyethyl)carboxymethylamine. Neither nitroso-2-hydroxymorpholine nor a sulfate of NDELA was detected.
将α-碳上标记有¹⁴C的N-亚硝基二乙醇胺(NDELA)以每只大鼠0.6至100毫克的不同剂量经口灌胃给予成年雄性Fischer 344大鼠。以¹⁴CO₂形式排泄的剂量比例很小,在24小时内,从最低剂量的0.27%到最高剂量的0.83%不等。在所有剂量下,约95%的放射性剂量(其中大部分是NDELA)在24小时内出现在尿液中,但代谢物的比例从最低剂量到最高剂量从7%增加到14%。给予100毫克和100微居里NDELA的大鼠肝脏中分离出的核酸的比活性非常低,且在治疗后6小时和24小时相同(70 dpm/毫克DNA,92 - 95 dpm/毫克RNA)。在核酸水解产物中初步鉴定出N⁷-(2-羟乙基)鸟嘌呤和O⁶-(2-羟乙基)鸟嘌呤,分别占DNA放射性的10%和4%;NDELA处理后6小时和24小时所发现的量之间没有差异。除NDELA外,从大鼠尿液中分离出四种成分,其中两种已鉴定。一种是NDELA的葡糖醛酸苷,另一种是N-亚硝基-N-(2-羟乙基)羧甲基胺。未检测到亚硝基-2-羟基吗啉或NDELA的硫酸盐。