[Enhancement of the toxic effect of endoxan after pretreatment with brain homogenates in rats].
Following monotherapy with cyclophosphamide rat leukemia cells (L 5222) survive only in the CNS, as has been described previously. Here we report on investigations performed to elucidate the influence of rat brain tissue on cyclophosphamide activity. It was found that the toxicity of cyclophosphamide is enhanced 5 fold after incubation with freshly prepared brain homogenate. In parallel experiments it was also found that cyclophosphamide preincubated with brain homogenates is therapeutically less effective toward L 5222 cells than cyclophosphamide alone. The incubation of cyclophosphamide with liver homogenate did not result in the same enhancement of cyclophosphamide toxicity nor in the decrease of therapeutic effects. The different influence of the two tissues on cyclophosphamide suggests two different metabolic mechanisms.
D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003520:Cyclophosphamide
Steigerung der toxischen Wirkung von Endoxan durch Einwirkung von Gehirnhomogenaten bei der Ratte.