3, 4, 5-Trihydroxybenzohydroxamic
acid (
VF 122), an inhibitor of
ribonucleotide reductase, killed rat
hepatoma 3924A cells in tissue cultured after 7 days of incubation. A concentration of 15 microM caused 50% inhibition of colony-forming ability (IC50). Under the same conditions,
hydroxyurea, also an inhibitor of
ribonucleotide reductase, had an IC50 of 52 microM. Treatment for 1 hr with
VF 122 of exponentially growing culture resulted in a biphasic exponential dose-response curve (Do = 0.5 mM, IC50 = 0.75 mM, and Do = 1.8 mM, IP = 0.8 mM). In plateau-phase cells, a threshold exponential curve was obtained (Do = 2.2 mM, Dq = 1.7 mM, and IC50 = 2.7 mM). Exponentially growing
hepatoma 3924A cells were more sensitive to
VF 122 than were plateau-phase cultures. In contrast,
hydroxyurea killed only exponentially growing 3924A
hepatoma cells, exhibiting an exponential plateau dose-response curve without achieving achieving an IC50 value at concentrations from 1 to 200 mM. In synchronized cultures,
VF 122 (1 MM for 1 hr) was toxic for cells in mid and late G1 phase, in early and mid S phase, and, to a lesser degree, in G2 phase,
Hydroxyurea (10 mM for 1 hr) killed cells only in S phase. Proliferating and resting
hepatoma 3924A cells recovered from sublethal and potentially lethal damage induced by
VF 122.