Mechanism of mutagen-induced deoxynucleoside triphosphate imbalance in Chinese hamster ovary (CHO-K1) cells

In previous reports, the authors demonstrated that exposure of Chinese hamster ovary cells (CHO-K1) to chemical carcinogen or radiation insults results in a transient deoxynucleoside triphosphate (dNTP) pool imbalance. Such an imbalance might be expected to affect the mutagenic response of cells to exposure by increasing the probability for base-misincorporation into de novo synthesized DNA and/or by exerting regulatory controls over the replicative response to exposure. Exposure to UV irradiation, a model mutagen, results in a rapid decrease (five- to ten-fold) in cellular dCTP and a concomitant increase (three- to sixfold) in dTTP, each observed within 10 minutes of exposure, and each persisting for several hours thereafter. However, the target and mechanism causing this response are not defined and, therefore, are presently the object of considerable study. A working hypothesis, now corroborated by data, is that radiation induces perturbations in selected enzyme activities which then perturb prevailing steady-state reaction equilibria, which, in turn, result in the imbalance the authors observe. Key enzyme activities were, therefore, examined in irradiated cells and compared to corresponding activities observed in unirradiated cells