THE EFFECT OF PURINE PHOSPHONOMETHOXYALKYL DERIVATIVES ON DNA-SYNTHESIS ON CHO CHINESE-HAMSTER CELLS

The inhibition of incorporation of H-3-thymidine and the changes of th e rate of nascent DNA chain elongation were investigated in CHO Chines e hamster cells treated with (S)-(3-hydroxy-2-phosphonomethoxypropyl) (HPMP) and N-(2-phosphonomethoxyethyl) (PME) derivatives of adenine (A ), guanine (G) and 2,6-diaminopurine (DAP). No direct correlation was observed in PME and HPMP derivatives between cytotoxicity, inhibition of H-3-thymidine incorporation and inhibition of nascent DNA chain elo ngation. The highest cytotoxicity and inhibition of DNA synthesis were caused by PMEG. The limited extent of inhibition of DNA elongation wa s encountered in the case of HPMPG and HPMPA. With PMEA, weak inhibiti on of elongation of DNA was observed only after a prolonged exposure ( 6 h). None of the investigated drugs induced DNA breaks.