Protective effect of cyloheximide on the response of rat hind limbs to x irradiation

Cycloheximide (CHM) is a known inhibitor of cytoribosomal protein synthesis and has been shown to delay transit of mammalian cells through the cell cycle. Previous studies have shown modification by CHM of the effect of radiation both in vitro and in vivo. To investigate a possible protective effect of the drug on the radiation response of normal tissue, skin reaction and structural damage in the hind limbs were scored in CHM-treated rats exposed to single dose of X irradiation. The drug had no effect on radiation reaction when given immediately before or after X-ray treatment. However, protection against both skin reaction and structural damage was observed when CHM was given at least 6 hr prior to irradiation with maximal protection observed at 12 hr. A similar protective action was seen for the protein synthesis inhibitor emetine. If CHM or other inhibitors of protein synthesis interrupt the normal cell cycle with resultant selective radioprotection of normal tissue, they may enhance the therapeutic effectiveness of radiation