Rosenkranz H S, Klopman G
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, PA 15261.
Mutat Res. 1992 Aug;282(4):241-6. doi: 10.1016/0165-7992(92)90129-6.
While there was no significant difference between the actual or predicted mutagenicity and clastogenicity of a group of chemicals carcinogenic only at the maximum tolerated dose (MTD) and a group of chemicals carcinogenic below the MTD, as a group, the chemicals carcinogenic below the MTD exhibited a significantly decreased LUMO (Lowest Unoccupied Molecular Orbital) energy, indicative of increased electrophilicity (i.e. DNA reactivity). These findings suggest that chemicals carcinogenic only at the MTD either require increased doses of "weak" electrophiles to be carcinogenic or that they may act by a "non-genotoxic" mechanism.
仅在最大耐受剂量（MTD）时致癌的一组化学物质与在MTD以下致癌的一组化学物质，其实际或预测的致突变性和染色体断裂活性之间没有显著差异，但总体而言，在MTD以下致癌的化学物质表现出最低未占分子轨道（LUMO）能量显著降低，这表明亲电性增加（即DNA反应活性增加）。这些发现表明，仅在MTD时致癌的化学物质要么需要增加“弱”亲电试剂的剂量才能致癌，要么它们可能通过“非遗传毒性”机制起作用。
