DNA modification induced by 6-mercaptopurine riboside in murine embryos.
The cytostatic drug 6-mercaptopurine riboside (6-MPr) was investigated in mice in order to test the hypothesis that the teratogenicity of this antimetabolite is paralleled by an incorporation into the DNA of the embryos during organogenesis. DNA modification in the embryos was analysed 4 h following s.c. administration of [35S]-labelled 6-MPr to the dams on day 11 of pregnancy. The DNA of the embryos was isolated and hydrolysed to the bases by formic acid. Following separation by cation-exchange HPLC 6-thioguanine was found in the hydrolysate. Quantitation was performed by liquid scintillation counting. Evaluations of 6 doses in the range of 8-25 mg/kg were performed. An incorporation rate of 6-thioguanine from 32-56 pmol per mumol guanine was found in the DNA of the embryos. These findings suggest that, similar to the previously studied alkylating agents, the teratogenicity of 6-MPr may be, at least in part, induced via DNA modification of the embryos.
Platzek
T
T
Max-von-Pettenkofer-Institut, Bundesgesundheitsamt, Berlin, Germany.
Schwabe
R
R
Rahm
U
U
Bochert
G
G
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000302:isolation & purification; D004622:Embryo, Mammalian; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D013462:Sulfur Radioisotopes; D013723:Teratogens / Q000493:pharmacokinetics / Q000633:toxicity*; D013866:Thioguanine / Q000633:toxicity; D013868:Thioinosine / Q000493:pharmacokinetics / Q000633:toxicity*
D013462:Sulfur Radioisotopes; D013723:Teratogens; D013868:Thioinosine; D004247:DNA; D013866:Thioguanine