Radiolabeling revisited: metabolic labeling with (35)S-methionine inhibits cell cycle progression, proliferation, and survival.

Metabolic labeling of cells with low-energy beta-emitting radioisotopes such as [(35)S]methionine is often used to follow the biosynthesis, maturation, and degradation of proteins in vivo. Such techniques have generally been assumed to be relatively nonperturbing to the cell. The results presented here indicate that metabolic labeling of cells with [(35)S]methionine under standard experimental conditions can inhibit cell progression into mitosis, cause cell cycle arrest, inhibit cell proliferation in both short-term and colony-forming assays, alter cell morphology, and induce apoptosis over the course of several days. These results thus suggest the need for caution in interpretation of studies using such methods, especially if the experiments rely on the normal progression of the cell cycle or are intended to monitor events occurring in a normally proliferating cell.