C. Young, G. Schochetman, S. Hodas
Mar 1, 1967
Citations
0
Influential Citations
96
Citations
Quality indicators
Journal
Cancer research
Abstract
Summary The following compounds inhibited incorporation of thymidine-3H into the DNA of HeLa cells without significantly impairing cellular incorporation of uridine-3H into RNA or leucine-3H into protein; they are listed in order of potency. Dihydroxyurea > N-methylhydroxyurea > N-acetylhydroxyurea = hydroxyurea = N-hydroxyguanidine = N-hydroxyurethane = N-ethylhydroxyurea > 3-phenyl-1-hydroxyurea = formamidoxime > N-methylacetohydroxamic acid = N-methylhydroxylamine > acetohydroxamic acid. Hydroxylamine, N-hydroxyglycine amide and 3-phenyl-1-hydroxy-2-thiourea inhibited incorporation of all three labeled precursors. Methoxyamine, methoxyurea, and N-methylmethoxyurea had no effect upon thymidine uptake. Addition of three deoxyribonucleosides, deoxyadenosine (0.1 mm), deoxyguanosine (0.1 mm), and deoxycytidine (1.0 µm), to the culture medium provided partial protection against the inhibitory effects of hydroxyurea, hydroxyurethane, acetohydroxamic acid, hydroxyguanidine, formamidoxime, and N-methylhydroxylamine. The data suggest that all of these agents inhibit a reaction in the biosynthesis of deoxyribonucleotides from ribonucleotides. The relationship between chemical structure and inhibitory activity is discussed and some possible inhibitory mechanisms examined.