Time-specific occurrence of alopecia in neonatal C57BL mice treated with N-methyl-N-nitrosourea and the therapeutic efficacy of tacrolimus hydrate.
Alopecia was induced in male and female neonatal C57BL mice by a single intraperitoneal injection of 60 mg/kg N-methyl-N-nitrosourea (MNU). MNU administration was most effective in the 8-day-old mice and less effective in the 5-day-old mice (at active and early anagen stages of the first hair cycle, respectively). No alopecia was seen in the day 14 MNU-treated animals (at telogen stage of the first hair cycle). MNU effectively induced hair follicular cell apoptosis at the anagen stage by up-regulation of Bax protein without down-modulation of Bcl-2 protein. In day 8 MNU-treated mice, the immunosuppressive agent 0.01% tacrolimus hydrate (FK506), when topically applied for 5 days from 1 day after MNU treatment (before the occurrence of alopecia), decreased the severity of alopecia. However, it did not stimulate hair growth when applied for 5 days from 20 days of age (after occurrence of alopecia).
Yoshizawa
K
K
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka, Japan.
Nambu
H
H
Yamamoto
D
D
Yang
J
J
Kiyozuka
Y
Y
Shikata
N
N
Tsubura
A
A
D000477:Alkylating Agents / Q000633:toxicity*; D000505:Alopecia / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
D000477:Alkylating Agents; C494827:Bax protein, mouse; D007166:Immunosuppressive Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008770:Methylnitrosourea; D016559:Tacrolimus