CPT-11 alters the circadian rhythm of dihydropyrimidine dehydrogenase mRNAin mouse liver

Citation
M. Shimizu et al., CPT-11 alters the circadian rhythm of dihydropyrimidine dehydrogenase mRNAin mouse liver, JPN J CANC, 92(5), 2001, pp. 554-561
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
JAPANESE JOURNAL OF CANCER RESEARCH
ISSN journal
0910-5050 → ACNP
Volume
92
Issue
5
Year of publication
2001
Pages
554 - 561
Database
ISI
SICI code
0910-5050(200105)92:5<554:CATCRO>2.0.ZU;2-J
Abstract
Combination chemotherapy consisting of 5-fluorouracil (5-FU) and 7-ethyl-10 -[4-( 1-piperidino)-1-piperidino]carboxycamptothecin (CPT-II) is a promisin g regimen for gastrointestinal cancer. The circadian-dependent efficacy and toxicity of 5-FU are related to the circadian variation in the activity of dihydropyrimidine dehydrogenase (DPD), which is a rate-limiting enzyme in the pryrimidine catabolic pathway. To optimize the schedule of the CPT-II p lus 5-FU combination, we investigated the effect of CPT-11 on the circadian rhythm of DPD in vivo. In control mice, the DPD mRNA level in the liver wa s significantly higher at 14:00 than that at 02:00, After intravenous admin istration of CPT-11 (30 mg/kg) at 20:00, the circadian rhythm of the DPD mR NA level in the liver was no longer observed 18 h later (14:00), but it was unaffected 6 and 18 h later (at 14:00 and 02:00) when CPT-II was given at 08:00, In addition, a dose-dependent lengthening of the period of the circa dian rhythm of DPD was observed for 42 h after intravenous injection of CPT -11 at 20:00, The levels of DPD protein and activity at 21 h after administ ration of CPT-11 (at 17:00) were significantly higher than at 9 h (at 05:00 ), These results suggest that CPT-11 may influence the circadian rhythm of DPD at the transcriptional level. Modulation of the circadian rhythm of DPD by CPT-11 mag be a factor in optimizing the combination of 5-FU and CPT-11 .