Reddy T V, Weisburger E K, Thorgeirsson S S
J Natl Cancer Inst. 1980 Jun;64(6):1563-9. doi: 10.1093/jnci/64.6.1563.
The Salmonella mutagenesis test system was used to evaluate the in vitro mutagenic potency of N-2-fluorenylacetamide (2-FAA) and N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) mediated by liver and kidney subcellular fractions from X/Gf mice, a strain resistant to 2-FAA carcinogenesis. Pretreatment of the mice with the microsomal inducers 3-methylcholanthrene (MCA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased the number of revertants from both liver and kidney fractions. Mutagenicity of N-OH-2-FAA mediated by liver or kidney microsomes was partially inhibited at 0.001--0.1 microM Paraxon (diethyl-p-nitrophenyl phosphate), an inhibitor of deacetylase enzyme, and the inhibition was complete (98%) in microsomes from control mice (100 microM Paraoxon). Conversely, the liver and kidney microsomal fractions from MCA- and TCDD-treated X/Gf mice were less sensitive to Paraoxon. The inhibition of kidney or liver cytosol-mediated N-OH-2-FAA mutagenicity by Paraoxon was less than that observed with the microsomal fraction (50% inhibition at 1 x 10(-7) and 1 x 10(-5) M Paraoxon, respectively). The mutagenicity of 2-FAA and N-OH-2-FAA mediated by liver or kidney subcellular fractions from X/Gf mice and its response to inducers and inhibitors of mutagenic activation processes appear similar to those observed in species both resistant (cotton rat) and sensitive (Sprague-Dawley rat, NIH Swiss mice) to 2-FAA carcinogenesis.
沙门氏菌诱变试验系统用于评估由X/Gf小鼠（一种对2-乙酰氨基芴致癌作用具有抗性的品系）的肝和肾亚细胞组分介导的N-2-芴基乙酰胺（2-FAA）和N-羟基-N-2-芴基乙酰胺（N-OH-2-FAA）的体外诱变效力。用微粒体诱导剂3-甲基胆蒽（MCA）和2,3,7,8-四氯二苯并-对-二恶英（TCDD）对小鼠进行预处理，可增加来自肝脏和肾脏组分的回复突变体数量。在0.001--0.1微摩尔对氧磷（二乙基对硝基苯基磷酸酯）（一种脱乙酰酶抑制剂）存在下，由肝脏或肾脏微粒体介导的N-OH-2-FAA的诱变性受到部分抑制，而在来自对照小鼠的微粒体中（100微摩尔对氧磷）抑制作用完全（98%）。相反，经MCA和TCDD处理的X/Gf小鼠的肝脏和肾脏微粒体组分对对氧磷的敏感性较低。对氧磷对肾脏或肝脏胞质溶胶介导的N-OH-2-FAA诱变性的抑制作用低于在微粒体组分中观察到的抑制作用（分别在1×10⁻⁷和1×10⁻⁵ M对氧磷时抑制50%）。由X/Gf小鼠的肝脏或肾脏亚细胞组分介导的2-FAA和N-OH-2-FAA的诱变性及其对诱变激活过程的诱导剂和抑制剂的反应，与在对2-FAA致癌作用具有抗性（棉鼠）和敏感（斯普拉格-道利大鼠、NIH瑞士小鼠）的物种中观察到的情况相似。
