Barale R, Rusciano D, Stretti G, Zucconi D, Monaco M, Mosesso P, Principe P
Mutat Res. 1983 Nov;111(3):295-312. doi: 10.1016/0027-5107(83)90028-3.
The present paper assesses the most suitable conditions for metabolic activation with yeasts in vitro, at least as far as cyclophosphamide (Cy) is concerned. These include treatment time, incubation temperature, the amounts of S9 and cofactors. Particular attention is devoted to the use of various solvents, showing that their use can considerably affect the mutagenic response of the chemical being tested. It also examines the effects of enzyme inducers (by using S9 from rats and mice) such as phenobarbital (PB) and 5,6-benzoflavone (BF) administered separately or together. The metabolizing capability of other organs such as the lungs and kidneys is also determined. All these data are compared with Cy genotoxicity (in vivo) evaluated by the intrasanguineous host-mediated assay and by recovering the yeast target cells from the liver, lung and kidneys. The most striking effects are that, in vitro, PB greatly enhances Cy genotoxicity, whilst in vivo it substantially reduces it.
本论文评估了体外使用酵母进行代谢活化的最合适条件，至少就环磷酰胺（Cy）而言。这些条件包括处理时间、孵育温度、S9和辅因子的量。特别关注了各种溶剂的使用，结果表明其使用会显著影响受试化学品的诱变反应。论文还研究了酶诱导剂（通过使用大鼠和小鼠的S9）单独或联合使用时的影响，如苯巴比妥（PB）和5,6-苯并黄酮（BF）。还测定了其他器官如肺和肾的代谢能力。所有这些数据都与通过血内宿主介导试验评估的Cy体内遗传毒性以及从肝脏、肺和肾中回收酵母靶细胞的结果进行了比较。最显著的影响是，在体外，PB大大增强了Cy的遗传毒性，而在体内，它却显著降低了这种毒性。
