Aphidicolin sensitivity of variant 3T6 cells selected for changes in ribonucleotide reductase

Two mouse fibroblast lines (3T6-HU-11 and $\text{3T6-CA}\text{dA}$) selected earlier for changes in either of the two subunits (M1 or M2) of ribonucleotide reductase showed an increased resistance to aphidicolin, a known inhibitor of DNA polymerase α. In both lines resistance is in all probability caused by overproduction of dNTPs. HU-11 overproduces an active M2 subunit, has an expanded dATP pool and shows a 2-fold increase in resistance to aphidicolin. $\text{CA}\text{dA}$ is mutated in the regulatory M1 subunit, overproduces both dATP and dCTP and shows a sevenfold increased resistance. Addition of aphidicolin resulted in a rapid contraction of the dCTP pool, but not of other dNTP pools. We speculate that these effects might be linked to a regulatory function of dCTP, or a compound derived from it.