Pitfalls in the interpretation of whole-body autoradiograms: long-time retention in brain and adrenal cortex caused by metabolic incorporation of 14C from various labelled xenobiotics.
The long-time retention of radioactivity in mice was studied by whole-body autoradiography after administration of 1-14C-alkanes (C12 and C16), 1-14C-polychlorododecanes (56 and 68% Cl w/w), U-14C-polychlorohexadecane (23% Cl w/w), ethyl-14C-phenacetin and ring-3H-phenacetin. All the labelled xenobiotics, except the high-chlorinated (68% Cl) polychloroalkane and the ring-3H-phenacetin, gave rise to long-time (12-60 days) retention of radioactivity in the central nervous system and in the adrenal cortex; the distribution of radioactivity within the brain corresponded to the stain intensity of myelin stained sections. Administration of 1-14C-fatty acids (C12 and C16) and 1-14C-acetylcoenzyme A gave a similar distribution pattern. The lipophilic radioactivity in brain and adrenal tissue was extracted and separated with thin-layer chromatography. In the adrenal extracts, the label co-chromatography mainly with cholesteryl ester, and in the brain extracts with cholesterol and with more polar lipids (mainly phosphatidyl-choline and -ethanolamine). The brain homogenate contained a non-extracted, probably proteinaceous, residue, with comparably high radioactivity. The results show that several 14C-labelled xenobiotics which give long time retention of radioactivity in the adrenal cortex and brain, are degraded to intermediates with the possibility to become incorporated into endogenous substances. The high-chlorinated alkane (1) and ring-3H-phenacetin (2) did not give such long time retention due to its persistance towards degradation (1), and lack of labelling of the degradable part of the molecule (2). It is concluded that erroneous interpretations can be drawn from distribution studies if the routes of degradation and positions of label of the 14C-labelled compounds are not considered.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002855:Chromatography, Thin Layer; D005260:Female; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010615:Phenacetin / Q000494:pharmacology; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D010615:Phenacetin