Chronomodulatory effect of cyclosporine upon survival of DBA mice with L1210 leukemia.
A circadian stage-dependent anti-tumor effect of cyclosporine was tested on 268 female DBA mice, 9-10 weeks of age. The mice were kept in 6 different environmental chambers on regimens of 12h of light alternating with 12h of darkness, staggered by 4h: they were inoculated intraperitoneally with 2 X 10(5) L1210 cells at one of 6 different circadian stages. At the same circadian stage, starting 48h after inoculation, for 4 days, each mouse received the vehicle, a fixed dose of cyclosporine (15 mg/kg b.w.), a varying dose of cyclosporine 5, 10, 20 and 25 mg/kg b.w.) or no treatment. Cyclosporine prolonged survival time in a circadian stage dependent fashion (p less than 0.01), as shown by an analysis of variance and by cosinor analysis (mesor = 8.45h; amplitude = 5.45h; acrophase = 12 HALO). Cyclosporine thus acts, in a feed-sideward, as a chronomodulator of the interaction between the tumor and its host.
D000818:Animals; D002940:Circadian Rhythm; D003524:Cyclosporins / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D008811:Mice, Inbred DBA
D003524:Cyclosporins