The effects of a leukaemia-controlling dose of acivicin on murine splenic lymphocytes in vitro and in vivo.
The development of successful chemotherapy for cancers, including leukaemia, is based on the exploitation of significant toxic differentials of the agents, between the cancer cells and their normal counterparts. A concentration of 0.1 mumol/L of the amino acid analogue acivicin (L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid) was sufficient to inhibit [3H]-DNA synthesis in mitogen stimulated murine splenic lymphocytes and WEHI 7.1 murine leukaemic cells in vitro, at glutamine concentrations up to 0.5 mmol/L. However, at concentrations of glutamine of 1.0 mmol/L and above, more acivicin was required to inhibit WEHI 7.1 cells than to inhibit the splenic lymphocytes. At 1.0 mmol/L glutamine, 18 h of exposure to an optimal inhibitory concentration of acivicin (0.5 mumol/L) in vitro was sufficient to inhibit [3H]-DNA synthesis in the mitogen stimulated lymphocytes, whereas 24 h of exposure to an optimal inhibitory acivicin concentration of 2.0 mumol/L was required for inhibition of [3H]-DNA synthesis in the WEHI 7.1 leukaemic cells. When an acivicin inoculation regime that was sufficient to control the growth of intraperitoneally (i.p.) implanted WEHI 7.1 leukaemic cells was administered to Balb/c mice, the primary immune response was significantly inhibited to an antigen given either during or after the acivicin treatment. These results indicate that lymphocytes replicating in vivo in a specific primary immune response could be as sensitive to acivicin as leukaemic cells.
Griffiths
M
M
University Department of Microbiology, Queen Elizabeth II Medical Centre, Nedlands, Western Australia.
Keast
D
D
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004351:Drug Resistance; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D007075:Immunoglobulin M; D007555:Isoxazoles; C006303:acivicin