Abstract
The chromosome-damaging effect of 6-mercaptopurine (6-MP) was investigated in bone marrow cells of rats, Chinese hamsters, and mice after single intraperitoneal injections of doses from 3.125 to 250 mg/kg, and after multiple applications of 10, 25, 50, and 125 mg/kg.
The optimal time of investigation after single administration in these studies was 48 hrs after treatment for all 3 species. A nearly linear dose-response relationship with a low quadratic component was observed.
The “critical dose” for all 3 species was 12.5 mg 6-MP/kg. However, mice generally demonstrated the highest sensitivity to the “clastogenic” effect of 6-MP. In agreement with results of acute toxicity studies, Chinese hamsters generally were less (and rats least) sensitive than the mouse to chromosomal damage induced by higher doses of 6-MP. After repeated treatment with low doses, the chromosomedamaging effect of 6-MP was less pronounced than after one single administration of a large dose equalling the total amount of substance applied in chronic treatment.
Zusammenfassung
Knochenmarkzellen von Maus, Ratte und chinesischem Hamster wurden nach einmaliger intraperitonealer Injektion von 6-Mercaptopurin (6-MP) für den Dosisbereich von 3,125 bis 250 mg/kg und nach mehrmaliger Applikation von 10, 25, 50 und 125 mg/kg auf Chromosomenaberrationen hin untersucht. Für alle 3 Species lag der optimale Untersuchungszeitpunkt bei einmaliger Applikation 48 Std nach der Injektion.
Die Dosis-Wirkungsbeziehung war fast linear mit einer geringen quadratischen Komponente. Die „kritische Dosis” für alle 3 Tierarten betrug 12,5 mg/kg. Allgemein jedoch zeigten Mäuse die höchste Empfindlichkeit gegenüber der clastogenen Wirkung von 6-MP. Die chromosomenschädigende Wirkung höherer Dosen betreffend waren — in Übereinstimmung mit den toxikologischen Befunden —chinesische Hamster allgemein weniger empfindlich als die Maus und Ratten weniger empfindlich als chinesische Hamster.
Nach wiederholter Behandlung mit niedrigen Dosierungen war die clastogene Wirkung von 6-MP weniger ausgeprägt als nach einmaliger Injektion einer hohen Dosis, die der bei chronischer Behandlung applizierten Gesamtmenge entsprach.
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Frohberg, H., Schulze Schencking, M. In vivo cytogenetic investigations in bone marrow cells of rats, chinese hamsters and mice treated with 6-mercaptopurine. Arch Toxicol 33, 209–224 (1975). https://doi.org/10.1007/BF00311274
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DOI: https://doi.org/10.1007/BF00311274
Key words
- 6-Mercaptopurine
- in vivo Cytogenetics
- Bone Marrow
- Time Dependence
- Dose-Response Relationship
- Species Differences