Oberly T J, Hoffman W P, Garriott M L
Toxicology Research Laboratories, Lilly Research Laboratories, A Division of Eli Lilly and Company, Greenfield, IN 46140, USA.
Mutat Res. 1996 Aug 12;369(3-4):221-32. doi: 10.1016/s0165-1218(96)90027-0.
The L5178Y tk+/- mouse lymphoma assay (MLA) has been in use for more than 15 years as a tool for evaluating the mutagenic potential of various agents. As with other genetic toxicology test systems, one criterion for a positive response has been the requirement of at least a 2-fold increase in mutant frequency (MF) as compared to the respective MF of the solvent controls. More recently, an actual specific increase in MF has been proposed as a criterion for determining a positive response in the MLA; however, this may not be appropriate for laboratories with a low, yet stable, background MF. The twofold rule criterion was evaluated in our laboratory with 66 compounds. The mutagenic status of these compounds was previously determined in other test systems and at one or more laboratories, including Lilly Research Laboratories. The results of this evaluation demonstrate that the twofold rule is an effective method for identifying mutagenic agents in the MLA at LRL where a lower, yet acceptable, background mutation frequency is the norm. A small number of compounds (6) yielded results discordant with the literature; however, these compounds have been previously found to be either difficult to detect in genotoxic assays or to show specific sensitivity in the MLA.
L5178Y tk+/-小鼠淋巴瘤试验（MLA）作为评估各种试剂诱变潜力的工具已使用超过15年。与其他遗传毒理学测试系统一样，阳性反应的一个标准是与溶剂对照各自的突变频率（MF）相比，突变频率至少增加2倍。最近，有人提出将MF的实际特定增加作为确定MLA中阳性反应的标准；然而，这可能不适用于背景MF较低但稳定的实验室。我们实验室用66种化合物对两倍规则标准进行了评估。这些化合物的诱变状态先前已在其他测试系统以及包括礼来研究实验室在内的一个或多个实验室中确定。该评估结果表明，在背景突变频率较低但可接受的LRL，两倍规则是在MLA中识别诱变剂的有效方法。少数化合物（6种）产生了与文献不一致的结果；然而，这些化合物先前已被发现要么在遗传毒性试验中难以检测，要么在MLA中表现出特定敏感性。
