Visser A, Westra J G
Carcinogenesis. 1981;2(8):737-40. doi: 10.1093/carcin/2.8.737.
Male rats were treated with [ring-3H]N-acetyl-2-aminofluorene and sacrificed at different periods of time after a single i.p. dose. Chromatin was isolated from liver homogenates and treated with RNAse and proteinase K. The resulting crude DNA was purified as the N-hexadecyl-N-trimethylammonium salt. The amounts of 2-aminofluorene and N-acetyl-2-aminofluorene bound to carbon-8 of guanine were determined in the DNA via acid hydrolysis and high pressure liquid chromatography of the hydrolysate. These two major interaction products of the carcinogen decreased rapidly during the first 2 weeks but in the second 2 weeks the decrease of both interactions was much smaller and approximately 15% of the amount that was bound after 24 h remained persistently bound to the DNA. Differences in liver DNA binding after 24 h were observed between male rats of the strain R-Amsterdam (Wistar-related) and Sprague Dawley males. At equal dose levels of N-acetyl-2-aminofluorene, liver DNa of Sprague Dawley rats contained 1/3 of the amount of N-(guanin-8-yl)-2-aminofluorene and 1/2 of the amount of N-(guanin-8-yl)-N-acetyl-2-aminofluorene present in liver DNA of the R-Amsterdam strain.
雄性大鼠经腹腔注射单剂量[环-³H]N-乙酰-2-氨基芴处理,并在不同时间段处死。从肝脏匀浆中分离出染色质,并用核糖核酸酶和蛋白酶K处理。所得粗DNA被纯化为N-十六烷基-N-三甲基铵盐。通过对水解产物进行酸水解和高压液相色谱法,测定DNA中与鸟嘌呤的碳-8位结合的2-氨基芴和N-乙酰-2-氨基芴的量。在最初的2周内,致癌物的这两种主要相互作用产物迅速减少,但在接下来的2周内,两种相互作用的减少幅度要小得多,并且在24小时后结合的量中约有15%持续与DNA结合。在R-阿姆斯特丹品系(与Wistar相关)的雄性大鼠和Sprague Dawley雄性大鼠之间,观察到24小时后肝脏DNA结合存在差异。在N-乙酰-2-氨基芴剂量水平相等的情况下,Sprague Dawley大鼠肝脏DNA中N-(鸟嘌呤-8-基)-2-氨基芴的含量是R-阿姆斯特丹品系大鼠肝脏DNA中该物质含量的1/3,N-(鸟嘌呤-8-基)-N-乙酰-2-氨基芴的含量是其1/2。