Mutagenic and toxic effects of 4-hydroperoxycyclophosphamide and of 2,4-tetrahydrocyclohexylamine (ASTA-Z-7557) on human lymphocytes cultured in vitro.
Certain biological effects exerted by 4-hydroperoxycyclophosphamide and by 2,4-tetrahydrocyclohexylamine (ASTA-Z-7557), utilized in vitro in the therapy of leukemias and lymphomas to eliminate the occult tumor cells in autologous marrow transplantations, were studied in human lymphocytes cultured in vitro. The data show that these drugs exert mutagenic activity eliciting unscheduled DNA synthesis (reparative synthesis) after DNA damage and cause about tenfold higher frequency of sister chromatid exchanges than controls. Furthermore, they exert strong toxic effects, measured as tritiated thymidine uptake inhibition, on mitogen-stimulated dividing cells even if pretreated during the nonproliferative phase of the cell cycle in which the toxic activity of the drugs is not detectable. Data obtained with doses of the drugs similar to those used in the therapy are discussed in terms of the therapeutic use of these chemicals.
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000633:toxicity; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008677:Metaphase / Q000187:drug effects; D009153:Mutagens; D012854:Sister Chromatid Exchange / Q000187:drug effects
D009153:Mutagens; C037933:Asta Z 7557; D003520:Cyclophosphamide; C011272:perfosfamide