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

Mikiko Shimizu, T. Tamura, Y. Yamada, Y. Akiyama, N. Saijo, K. Nishio

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Combination chemotherapy consisting of 5-fluorouracil (5-FU) and 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carboxycamptothecin (CPT-11) is a promising 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 pyrimidine catabolic pathway. To optimize the schedule of the CPT-11 plus 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 was significantly higher at 14:00 than that at 02:00. After intravenous administration of CPT-11 (30 mg/kg) at 20:00, the circadian rhythm of the DPD mRNA 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-11 was given at 08:00. In addition, a dose-dependent lengthening of the period of the circadian 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 administration 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 may be a factor in optimizing the combination of 5-FU and CPT-11.

Original languageEnglish
Pages (from-to)554-561
Number of pages8
JournalJapanese Journal of Cancer Research
Volume92
Issue number5
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

irinotecan
Dihydrouracil Dehydrogenase (NADP)
Circadian Rhythm
Messenger RNA
Liver
Fluorouracil

Keywords

  • Circadian rhythm
  • CPT-11
  • Dihydropyrimidine dehydrogenase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Shimizu, M., Tamura, T., Yamada, Y., Akiyama, Y., Saijo, N., & Nishio, K. (2001). CPT-11 alters the circadian rhythm of dihydropyrimidine dehydrogenase mRNA in mouse liver. Japanese Journal of Cancer Research, 92(5), 554-561.

CPT-11 alters the circadian rhythm of dihydropyrimidine dehydrogenase mRNA in mouse liver. / Shimizu, Mikiko; Tamura, T.; Yamada, Y.; Akiyama, Y.; Saijo, N.; Nishio, K.

In: Japanese Journal of Cancer Research, Vol. 92, No. 5, 2001, p. 554-561.

Research output: Contribution to journalArticle

Shimizu, M, Tamura, T, Yamada, Y, Akiyama, Y, Saijo, N & Nishio, K 2001, 'CPT-11 alters the circadian rhythm of dihydropyrimidine dehydrogenase mRNA in mouse liver', Japanese Journal of Cancer Research, vol. 92, no. 5, pp. 554-561.
Shimizu M, Tamura T, Yamada Y, Akiyama Y, Saijo N, Nishio K. CPT-11 alters the circadian rhythm of dihydropyrimidine dehydrogenase mRNA in mouse liver. Japanese Journal of Cancer Research. 2001;92(5):554-561.
Shimizu, Mikiko ; Tamura, T. ; Yamada, Y. ; Akiyama, Y. ; Saijo, N. ; Nishio, K. / CPT-11 alters the circadian rhythm of dihydropyrimidine dehydrogenase mRNA in mouse liver. In: Japanese Journal of Cancer Research. 2001 ; Vol. 92, No. 5. pp. 554-561.
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