Circadian rhythm in toxic effects of cystemustine in mice: Relevance for chronomodulated delivery

✍ Scribed by Nathalie Martineau-Pivoteau; Francis Levi; Christine Rolhion; Fabrice Kwiatkowski; Guy Lemaigre; Elisabeth Filipski; Philippe Chollet

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 592 KB
• Volume: 68
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19961127)68:5<669::aid-ijc18>3.0.co;2-x

✦ Synopsis

Cystemustine is a new nitrosourea with high anti-tumor activity and a short plasma half-life in mice. The influence of circadian dosing time upon its toxicities was first investigated in a total of 368 synchronized male B6DZFI mice. Late survival rate varied from 4% in mice receiving a single dose of cystemustine (conventional lethal dose 5 0 % ) at 7 hours after !ight onset (HALO) up to 88% in mice treated at I 5 or at I9 HALO. Target organ toxicities (bone marrow, circulating blood cells, spleen, colon and duodenum) were studied following a single slightly lower dose of cystemustine. Leukopenia was the major hematologic effect encountered. Leukocyte count nadir occurred 7 days after injection and was lowest following cystemustine at 7 HALO as compared to 13 or 19 HALO. Recovery was faster after cystemustine at 19 HALO as compared to other dosing times.