RESUMO
Circadian clock genes have been identified in humans but information regarding their expression has remained very limited. However from a basic point as well as in a diagnostic and therapeutic perspective, it is important to evaluate molecular clock gene expression. Peripheral blood mononuclear cells represent an ideal material to investigate non-invasively the human clock at the molecular level. Several studies including ours reported rhythmic expression of clock genes in these cells, with significant intersubject variability of expression. In addition, our results reveal the existence of different chronotypes of clock gene expression patterns and suggest specific regulatory mechanisms in these human cells as compared to other peripheral tissues.
Assuntos
Relógios Biológicos/genética , Ritmo Circadiano/genética , Regulação da Expressão Gênica , Leucócitos Mononucleares/fisiologia , Fatores de Transcrição ARNTL , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Ciclo Celular/genética , Humanos , Proteínas Nucleares/genética , Proteínas Circadianas Period , Fatores de Transcrição/genéticaRESUMO
Dihydropyrimidine deshydrogenase (DPD) is the rate limiting enzyme of 5-fluorouracil (5-FU) catabolism and its activity is generally determined in peripheral blood mononuclear cells. Several studies have highlighted interactions between toxicities to 5-FU and a DPD activity deficiency. Circadian variations in 5-FU anabolism enzymes are suggested. Circadian variations in 5-FU catabolism enzymes, and especially for DPD in healthy subjects or patients, have shown in some cases circadian variations in DPD activity but with different peak times. Based on this knowledge, chronomodulated therapy for the association 5-FU-folinic acid with maximal delivery rate in the first half of the night was shown clearly to be 5 times less toxic than control flat therapy. Nevertheless, in the most active chronotherapy pattern, 30% of the patients have also toxicities. However the timing of the individual peak of DPD activity remains controversial.