In vivo effects of T-2 mycotoxin on synthesis of proteins and DNA in rat tissues.
Rats were given an ip injection of T-2 mycotoxin (T-2), the T-2 metabolite, T-2 tetraol (tetraol), or cycloheximide. Serum, liver, heart, kidney, spleen, muscle, and intestine were collected at 3, 6, and 9 hr postinjection after a 2-hr pulse at each time with [14C]leucine and [3H]thymidine. Protein and DNA synthesis levels in rats were determined by dual-label counting of the acid-precipitable fraction of tissue homogenates. Rats given a lethal dose of T-2, tetraol, or cycloheximide died between 14 and 20 hr. Maximum inhibition of protein synthesis at the earliest time period was observed in additional rats given the same lethal dose of the three treatments and continued for the duration of the study (9 hr). With sublethal doses of T-2 or tetraol, the same early decrease in protein synthesis was observed but, in most of the tissues, recovery was seen with time. In the T-2-treated rats. DNA synthesis in the six tissues studied was also suppressed, although to a lesser degree. With sublethal doses, complete recovery of DNA synthesis took place in four of the six tissues by 9 hr after toxin exposure. The appearance of newly translated serum proteins did not occur in the animals treated with T-2 mycotoxin or cycloheximide, as evidenced by total and PCA-soluble serum levels of labeled leucine. An increase in tissue-pool levels of free leucine and thymidine in response to T-2 mycotoxin was also noted. T-2 mycotoxin, its metabolite, T-2 tetraol, and cycloheximide cause a rapid inhibition of protein and DNA synthesis in all tissue types studied. These results are compared with the responses seen in in vitro studies.
Thompson
W L
WL
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701-5011.
Wannemacher
R W
RW
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis*; D002250:Carbon Radioisotopes; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007930:Leucine / Q000097:blood / Q000378:metabolism; D008297:Male; D051381:Rats; D013605:T-2 Toxin / Q000378:metabolism / Q000633:toxicity* / Q000031:analogs & derivatives; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D000596:Amino Acids; D001798:Blood Proteins; D002250:Carbon Radioisotopes; D014316:Tritium; C046700:T-2 tetraol; D004247:DNA; D003513:Cycloheximide; D007930:Leucine; D013605:T-2 Toxin; D013936:Thymidine