Barrat M A, Renée N, Mormont M C, Milano G, Levi F
Département de prothèses, faculté de chirurgie dentaire de Nice Sophia-Antipolis, avenue Diables-Bleus, 06000, Nice, France.
Pathol Biol (Paris). 2003 Jun;51(4):191-3. doi: 10.1016/s0369-8114(03)00035-x.
Dihydropyrimidine dehydrogenase (DPD) is the rate limiting enzyme of 5-fluoro-uracil (5-FU) catabolism. DPD rhythmicity, peak at 1:00 is an important determinant of 5-FU tolerability and has practical implications for the pattern of chronomodulated delivery of the drug. Maximal tolerated doses have been highed and anti-tumour activity also. But 30% patients have toxicities expressed by mucositis in oral mucosa.
Titrate DPD activity in oral mucosa in healthy subjects, in oral mucosa which is the target of 5-FU, at 10:00 and midnight could help to understand toxicities in patients.
Eight healthy subjects participated (information note signed by patients). One oral mucosa sample was drawn at 10:00 and an other at midnight. DPD activity was analyzed by a H.P.L.C. method.
DPD activity in oral mucosa varied from 0.004 to 0.13 nmol x min(-1) x mg(-1) prot at 10:00 and from 0.07 to 0.16 nmol x min(-1) x mg(-1) prot at midnight, with a 30% average relative increase from morning to midnight (range: -20% to +100%; statistical significant difference with P <0.073).
DPD circadian changes in healthy oral mucosa subjects remained to agree to mononuclear cell, with increase at midnight.
二氢嘧啶脱氢酶（DPD）是5-氟尿嘧啶（5-FU）分解代谢的限速酶。DPD节律性，1:00达到峰值，是5-FU耐受性的重要决定因素，并且对该药物的时间调制给药模式具有实际意义。最大耐受剂量已经提高，抗肿瘤活性也提高了。但是30%的患者出现口腔黏膜黏膜炎表现的毒性。
在健康受试者的口腔黏膜（5-FU的作用靶点）中，于10:00和午夜测定DPD活性，可能有助于了解患者的毒性情况。
8名健康受试者参与（患者签署知情同意书）。在10:00采集一份口腔黏膜样本，在午夜采集另一份。通过高效液相色谱法分析DPD活性。
口腔黏膜中的DPD活性在10:00时为0.004至0.13 nmol·min⁻¹·mg⁻¹蛋白，在午夜时为0.07至0.16 nmol·min⁻¹·mg⁻¹蛋白，从早晨到午夜平均相对增加30%（范围：-20%至+100%；P<0.073时有统计学显著差异）。
健康口腔黏膜受试者中DPD的昼夜变化与单核细胞的情况一致，午夜时增加。
