The effect of neomycin on RNA and protein synthesis in Chinese hamster cells cultured in vitro, 1971

Neomycin is an aminoglycoside of the streptomycin group of anti-biotics that is known to cause misreading of the genetic code in in vitro bacterial systems. In order to determine whether microbial antimetabolites have some effect on macromolecular biosynthesis of higher cells, the antibiotic neomycin was selected for this study with mammalian cells cultured jin vitro. Synchronized cultures of Chinese hamster cells were exposed to various concentrations of neomycin, ranging from 25 pg/ml that have been used for bacteria, to 100 and 200 pg/ml, for different time periods. Optical density determinations were made for RNA and protein content in control and neomycin-treated cells. [3 H]-uracil and [14 C]-valine incorporation into macromolecules was used to measure the rate of RNA and protein synthesis in the presence and in the absence of the antibiotic. Basically, what neomycin does is to inhibit protein synthesis by alteration of the translational process, with a secondary effect on the rate of RNA synthesis. The phase of growth of the cell population, rather than the length of the treatment, made a great difference in the percentage of inhibition observed. Comparative studies of neomycin, actinomycin and chloramphenicol indicate that the action of neomycin affects protein synthesis in a way that closely resembles the chloramphenicol effect. The immediate effect of short-term treatments with neomycin is highly reversible, but a long-term exposure to the drug finally destroys sensitive cells. The response of mammalian cells to neomycin is analogous to bacterial cells even at the gene level because in the course of this study neomycin-resistant and dependent cells were found along with the neomycin-sensitive Chinese hamster cells