Influence of cyclosporin A and alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on two rodent T-cell cancers in vivo.
We have examined the influence of cyclosporin A (CsA), administered together with the polyamine antimetabolite, alpha-difluoromethylornithine (DFMO), on growth of the Roser acute T-cell leukaemia in PVG rats and on growth of the EL4 lymphoma in C57BL/6 mice. CsA or DFMO alone, administered from the time of tumour injection, markedly reduced numbers of circulating lymphoblasts in leukaemic rats, although survival was prolonged only in those animals given DFMO. Drug combination further reduced blood-borne tumour cells, but had no additional effects on tumour growth within organs or on host survival, compared to that achieved with DFMO treatment alone. Neither CsA nor DFMO, administered from the time of tumour-cell injection, nor both drugs in combination, affected peritoneal growth of the EL4 lymphoma or organ infiltration. Host survival was prolonged by DFMO. As anticipated, DFMO inhibited polyamine synthesis in vivo, but the observed anti-tumour effect of CsA was not accompanied by an alteration in polyamine biosynthesis. By reducing polyamine synthesis, however, DFMO may enhance the vulnerability of those malignant T cells which are susceptible to the as yet unexplained selective inhibitory action of CsA in vivo.
Smart
L M
LM
Department of Pathology, Medical School, University of Aberdeen, Foresterhill, Scotland, UK.
MacLachlan
G
G
Wallace
H M
HM
Thomson
A W
AW
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003524:Cyclosporins / Q000008:administration & dosage*; D004357:Drug Synergism; D000518:Eflornithine / Q000008:administration & dosage*; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011073:Polyamines / Q000378:metabolism; D051381:Rats; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000473:pathology*
D003524:Cyclosporins; D011073:Polyamines; D000518:Eflornithine