Hepatic subcellular distribution of [3H]T-2 toxin.
The subcellular distribution of T-2 mycotoxin and its metabolites was studied in isolated rat livers perfused with [3H]T-2 toxin. After a 120-min perfusion, the distribution of radiolabel was to bile 53%, perfusate 38% and liver 7%. Livers were fractionated into mitochondria, endoplasmic reticulum (smooth and rough), plasma membrane and nuclei. Plasma membrane fractions contained 38% of the radiolabel within 5 min, decreasing to less than 1% at the end of the 120-min perfusion. Smooth endoplasmic reticulum contained 27% of the radiolabel by 5 min and increased to 43% over the 120-min perfusion. The mitochondrial fraction contained 3% of the radiolabel by 30 min and increased to 10% after 120-min perfusion. Label in the nuclear fraction remained constant at 7% from 30 to 120 min. By 15 min, only the parent toxin was detected in the mitochondrial fraction. In the other fractions, radiolabel was associated with HT-2, 4-deacetylneosolaniol, T-2 tetraol, and glucuronide conjugates. Glucuronide conjugates accounted for radiolabel eliminated via the bile. The time course for distribution of radiolabel in liver suggested an immediate association of [3H]T-2 with plasma membranes and a subsequent association of toxin and metabolites with endoplasmic reticulum, mitochondria and nuclei, the known sites of action of this toxin.
Pace
J G
JG
Pathophysiology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21701-5011.
Watts
M R
MR
D000818:Animals; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344; D012588:Scintillation Counting; D012717:Sesquiterpenes / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013605:T-2 Toxin / Q000378:metabolism*
D012717:Sesquiterpenes; D013605:T-2 Toxin