CORRELATION OF THE LIPOPHILICITY OF XENOBIOTICS WITH THEIR SYNERGISTIC EFFECTS OF DNA-SYNTHESIS IN HUMAN FIBROBLASTS

The binary combination effects on DNA synthesis of human fibroblasts w ere investigated using 2,4-D with 15 xenobiotics of different chemical substance classes. Results were compared with previous investigations on cell growth. Each of the 15 chemicals tested at their no effect co ncentrations (NOEC's) increased the effects of 2,4-D on DNA synthesis. Thereby, the EC(20) value of 2,4-D was reduced by approximately 40% i n the combinations. The NOEC's of the xenobiotics used in the combinat ions varied by a factor of 1,600 and depended strongly on the lipophil icity of the agents combined with 2,4-D. A significant statistical cor relation of r = 0.90 was found between the NOEC's of the 15 combined x enobiotics and their lipophilicity. The combination effects on DNA syn thesis were similar to those on cell growth. The regression lines of t he relationship between the NOEC's and lipophilicity in both assays sh owed only slight difference's in the slopes. This is an additional con firmation of our hypothesis oda facilitated uptake of 2,4-D in the bin ary combinations. Copyright (C) 1996 Elsevier Science Ltd