Specific association of T-2 toxin with mammalian cells.
The binding of radiolabeled T-2 toxin to a mammalian cell line derived from a Chinese hamster ovary (CHO) was studied. The toxin bound to, or was taken up by, cells in a time-, temperature- and concentration-dependent manner. The binding was saturable, of high affinity (Kd approximately 0.1 to 1 nM), reversible at 37 degrees (half-time approximately 2 hr), and specific. The kinetics of T-2-cell association and the rate of toxin-induced inhibition of protein synthesis closely paralleled one another. Likewise, the concentration-response for inhibition of protein synthesis and the toxin binding isotherm were similar. A synthetically derived epimer of T-2 bound less tightly to cells, but apparently to the same site as authentic T-2. The epimer was also less potent at inducing inhibition of protein synthesis. Two other trichothecene toxins, one more and one less toxic than T-2, blocked labeled T-2 binding to cells in a manner reflective of their protein synthesis inhibitory potencies. We conclude that the binding we defined is an accurate measure of the toxin responsible for inhibition of protein synthesis in CHO cells. The data also suggested that, at equilibrium, the interaction of T-2 with cells is not static, but is the sum of a continuous uptake and release process.
Department of Toxinology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21701-5011.
J L
JL
Middlebrook
D L
DL
Leatherman
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D014176:Protein Biosynthesis; D012717:Sesquiterpenes / Q000378:metabolism*; D013237:Stereoisomerism; D013605:T-2 Toxin / Q000378:metabolism* / Q000494:pharmacology; D013696:Temperature
D012717:Sesquiterpenes; D013605:T-2 Toxin