The tissue localization of m-AMSA and its effect on thymidine incorporation in various tissues in vivo.
The distribution of 14C-labelled m-AMSA was studied in rats and pigmented mice using whole body autoradiography. The agent rapidly disappeared from the blood, accumulating in significant amounts in large parenchymal organs, certain endocrine tissues, and the retina of the pigmented mouse eye. The hemopoietic and lymphoid tissues showed a moderate uptake of radioactivity with the highest concentration observed in the thymus. The autoradiograms indicated a rapid excretion of radioactivity via the liver, kidney and the glandular part of the gastric mucosa. The distribution pattern of label from 14C-m-AMSA remained unaffected by pretreatment of animals with high dose (500 mg kg-1 b.w.) of cytosine arabinoside. Injection of unlabelled m-AMSA (7 mg kg-1 b.w.) to growing rats 24 h before sacrifice resulted in a highly significant (P less than 0.001) inhibition of 3H-thymidine incorporation into the DNA of thymus and spleen. A less pronounced reduction was observed in the kidney, adrenal, lung and testes. The thymidine incorporation into the DNA of bone marrow was markedly suppressed when calculated per dry weight, but increased when related to the DNA content, suggesting early regeneration of the remaining cells. In contrast, no significant effects were observed on the DNA synthesis in small intestine and liver.
D000609:Aminoacridines / Q000378:metabolism* / Q000494:pharmacology; D000677:Amsacrine; D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D004261:DNA Replication / Q000187:drug effects*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014018:Tissue Distribution; D014316:Tritium
D000609:Aminoacridines; D002250:Carbon Radioisotopes; D000677:Amsacrine; D014316:Tritium; D013936:Thymidine