Is ribonucleotide reductase in Ehrlich ascites mammary tumour cells the target of a growth inhibitor purified from bovine mammary gland?

2'-deoxycytidine (dCyd), 2'-deoxyuridine (dUrd) and cytidine (Cyd) were found to relieve the inhibitory action by a factor, highly purified from bovine mammary gland, on the resumption of growth in vitro of stationary Ehrlich ascites mammary tumour cells. As described earlier, this effect is also achieved by insulin, proinsulin and epidermal growth factor and fetal calf serum. The effect of purine-2'-deoxyribonucleosides could not be properly assessed, because they were inhibitory themselves. Purine ribonucleosides as well as uridine and uracil were inactive. Because of the inactivity of the latter two compounds, the effect is attributed to an influence of the factor on the ribonucleotide reductase (RR) (and not on the de novo pyrimidine synthesis). The active nucleosides need not be present for the whole incubation time of 24 h; when treated for 4 h with the nucleosides, which are then removed before the addition of the factor, cells become insensitive against the latter. Again a similar effect has been described earlier for serum and insulin. The inhibitor of RR, hydroxyurea, prevents this specific effects of serum and (partially) insulin as well that of dCyd, also suggesting the involvement of RR in the factor action.