Takehisa S, Wolff S
Mutat Res. 1978 Nov;58(2-3):321-9. doi: 10.1016/0165-1218(78)90026-5.
Because short in vitro treatments of Chinese hamster cells with 2-aminofluorene and 2-acetylaminofluorene did not increase SCEs even in the presence of a metabolic activation system, experiments were carried out with rabbits to see if in vivo activation occurred. Rabbits injected with 2-AF could activate the compound and a transient dose-dependent increase in SCEs was found in peripheral lymphocytes cultured at various times after the injection. With 2-AAF, however, the response was more variable: some rabbits showed an increase immediately, but one showed an increase only after a subsequent injection. This indicated that among rabbits differences exist in their ability to detoxify 2-AAF. Because rabbits could activate the compounds, in vitro experiments were carried out to see if their lymphocytes responded differently from Chinese hamster cells and to see if the metabolic changes brought about by PHA stimulation affect the ability of the cells to activate the chemicals. The addition of PHA and the consequent metabolic stimulation do affect the induction of enzymes involved in the activation of 2-AF and 2-AAF. Benzo[alpha]pyrene, in contrast, can be activated by rabbit lymphocytes independently of PHA stimulation.
由于用2-氨基芴和2-乙酰氨基芴对中国仓鼠细胞进行短时间的体外处理，即使在有代谢活化系统存在的情况下也不会增加姐妹染色单体交换（SCEs），因此用兔子进行了实验，以观察体内是否发生活化。注射2-氨基芴（2-AF）的兔子能够活化该化合物，并且在注射后的不同时间培养的外周淋巴细胞中发现SCEs有短暂的剂量依赖性增加。然而，对于2-乙酰氨基芴（2-AAF），反应则更具变异性：一些兔子立即出现增加，但有一只兔子仅在随后的一次注射后才出现增加。这表明兔子之间在解毒2-AAF的能力上存在差异。由于兔子能够活化这些化合物，因此进行了体外实验，以观察它们的淋巴细胞反应是否与中国仓鼠细胞不同，以及植物血凝素（PHA）刺激引起的代谢变化是否会影响细胞活化化学物质的能力。PHA的添加以及随之而来的代谢刺激确实会影响参与2-氨基芴（2-AF）和2-乙酰氨基芴（2-AAF）活化的酶的诱导。相比之下，苯并[a]芘可被兔子淋巴细胞独立于PHA刺激而活化。
