Pretreatment with 1,25(OH)2D3 protects from Cytoxan-induced alopecia without protecting the leukemic cells from Cytoxan.
The authors previously demonstrated that pretreatment with 1,25(OH)2D3 protects from Cytoxan-induced alopecia in the rat model. The current study was designed to investigate whether 1,25(OH)2D3 protects the transplantable rat chloroleukemia (C51) cells from the cytotoxic effects of Cytoxan. In vitro, 4-hydroperoxycyclophosphamide had a dose-dependent cytotoxic effect on C51 cells. In separate experiments, preincubation with 1,25(OH)2D3 did not protect the C51 cells from the cytotoxic effects of 4-hydroperoxycyclophosphamide. In vivo, 4 groups of 10 5-day-old rats were treated as follows: Groups 1 and 2 received 0.2 micrograms of 1,25(OH)2D3 topically in ethanol daily starting on day 5 through day 10. Groups 3 and 4 received ethanol topically similarly. On day 7, all rats received 1 x 10(5) C51 cells intraperitoneally. On day 11, groups 1 and 3 received 35 mg/kg Cytoxan intraperitoneally. All rats in groups 2 and 4 were dead of leukemia by day 34. In groups 1 and 3, only 1 of 10 and 2 of 10 rats died of leukemia, respectively. Alopecia developed in all rats in group 3. In contrast, all rats in group 1 were protected from Cytoxan-induced alopecia. These results indicate that, in vivo, pretreatment with 1,25(OH)2D3 does not protect the rat chloroleukemia cells from the cytotoxic effect of Cytoxan, while protecting from Cytoxan-induced alopecia.
Jimenez
J J
JJ
Department of Medicine, University of Miami School of Medicine, Florida 33101, USA.
Alvarez
E
E
Bustamante
C D
CD
Yunis
A A
AA
D000505:Alopecia / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D002117:Calcitriol / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D014407:Tumor Cells, Cultured
D003520:Cyclophosphamide; D002117:Calcitriol