Tinwell H, Lefevre P A, Ashby J
Zeneca Central Toxicology Laboratory, Alderley Park, Nr. Macclesfield, Ches., UK.
Mutat Res. 1994 Jun 1;307(2):501-8. doi: 10.1016/0027-5107(94)90261-5.
Young adult (approximately 8 w) and old (approximately 72 w) lac I transgenic mice have been exposed to a single oral dose of dimethyl nitrosamine (NDMA). 2.5 h later unscheduled DNA synthesis was observed in the liver of the young animals (19.5 NG; control value -3.4 NG). The frequency of lac I- mutations in the liver of the young animals was elevated 7, 10 and 20 days after dosing. A similar fold-increase in mutant frequency was seen 7 days after dosing the old animals. It is concluded that mutability of the genome of old animals is not significantly different to that of young animals. Aspects of the minimum Big Blue assay protocol are discussed, as are the differing perceptions of the role of the assay in carcinogen hazard assessment.
将年轻成年（约8周龄）和老年（约72周龄）的乳糖操纵子I转基因小鼠单次口服给予二甲基亚硝胺（NDMA）。2.5小时后，在年轻动物的肝脏中观察到了非预定DNA合成（19.5纳克；对照值为-3.4纳克）。给药后7天、10天和20天，年轻动物肝脏中乳糖操纵子I突变的频率升高。给老年动物给药7天后，突变频率也出现了类似的倍数增加。得出的结论是，老年动物基因组的可突变性与年轻动物没有显著差异。讨论了最小大蓝检测方案的各个方面，以及对该检测在致癌物危害评估中作用的不同看法。
