Metabolism of a new radioprotector; S-acetyl-N-glycyl cysteamine. II. Main tissue metabolites in mice bearing EMT6 tumours.
1. The major tissue metabolites of the radioprotector S-acetyl-N-glycl cysteamine (I) labelled with 14C on the cysteamine group, were quantified and identified in normal tissues and EMT6 tumours implanted in mice, by chromatographic comparison with authentic reference compounds. 2. In all tissues the radioprotector undergoes rapid deacetylation and hydrolysis leading to the formation of cysteamine, which is the main metabolite involved in radioprotection. A major part of this metabolite is reversibly inactivated by binding to endogenous SH. 3. The differential radioprotection of healthy tissues versus EMT6 tumour is explained both by a lower uptake of radioprotector, and a weaker deacetylation and hydrolysis rate, in the tumour cells.
Maurizis
J C
JC
INSERM U 71, Clermont-Ferrand, France.
Madelmont
J C
JC
Godeneche
D
D
Moreau
M F
MF
Oiry
J
J
Imbach
J L
JL
Veyre
A
A
Meyniel
G
G
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003543:Cysteamine / Q000378:metabolism / Q000031:analogs & derivatives; D005998:Glycine / Q000378:metabolism / Q000031:analogs & derivatives; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism*; D011485:Protein Binding; D011837:Radiation-Protective Agents / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; D003543:Cysteamine; C058950:S-acetyl-N-glycylcysteamine; D005998:Glycine