Aspects of the biochemical pharmacology of cytembena

Cytembena, at low concentrations, caused an inhibition of the in vitro growth of L1210 mouse leukaemia cells which could not be reversed by reduced folates, purines, amino acids or deoxyribonucleosides. Invitro experiments with a number of enzymes of folate metabolism produced no evidence that this drug acts as an anti-folate in mammalian tumor colls. However, Cytembena, in therapeutic doses, caused a rapid and extensive inhibition of DNA biosynthesis. There was no inhibition of RNA biosynthesis, but at high doses some inhibition of protein biosynthesis was observed. Deoxyribonucleoside triphosphates accumulated in the presence of Cytembena, suggesting that the inhibition of DNA biosynthesis was at the polymerization stage. However, in vitro experiments failed to demonstrate any direct interaction of Cytmebena with either DNA or DNA polymerase.