Sensitivity of murine B- and T-lymphocytes to oxazaphosphorine and non-oxazaphosphorine nitrogen mustards.
The relative sensitivities of murine B- and T-lymphocytes to the oxazaphosphorine nitrogen mustards, cyclophosphamide and ASTA Z 7557, and to the non-oxazaphosphorine nitrogen mustards, melphalan and chlorambucil, in vivo, were determined. B- and T-lymphocytes were defined by selective mitogen-induced proliferation. Lipopolysaccharide (LPS)-induced B-lymphocytes were approximately twice as sensitive to the cytotoxic effects of cyclophosphamide and ASTA Z 7557 as were phytohemagglutinin (PHA)- and concanavalin A (Con A)-induced T-lymphocytes. LPS-induced B-lymphocytes and PHA-induced T-lymphocytes were approximately equisensitive to the cytotoxic action of melphalan and chlorambucil, but the former were somewhat more sensitive to these agents than were Con A-induced T-lymphocytes. The relative sensitivities of murine B- and T-lymphocytes to ASTA Z 7557 and the non-oxazaphosphorine metabolite of cyclophosphamide, phosphoramide mustard, ex vivo, were also determined. LPS-induced B-lymphocytes were approximately twice as sensitive to the cytotoxic action of ASTA Z 7557 as were PHA- and Con A-induced T-lymphocytes. The three mitogen-induced lymphocyte populations were approximately equisensitive to the cytotoxic action of phosphoramide mustard. These observations suggest that the differential effect of cyclophosphamide on murine B- and T-lymphocytes is uniquely exhibited by oxazaphosphorine nitrogen mustards. Furthermore, the results suggest that 4-hydroxycyclophosphamide is the cyclophosphamide metabolite that mediates the differential immunotoxic effect of the parent compound.
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D002699:Chlorambucil / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008558:Melphalan / Q000494:pharmacology*; D051379:Mice; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D008070:Lipopolysaccharides; D009588:Nitrogen Mustard Compounds; D009943:Organophosphorus Compounds; D010835:Phytohemagglutinins; D003208:Concanavalin A; D002699:Chlorambucil; C037933:Asta Z 7557; D003520:Cyclophosphamide; D008558:Melphalan