Ponsa Immaculada, Ramos-Quiroga Josep Antoni, Ribasés Marta, Bosch Rosa, Bielsa Anna, Ordeig Maria Teresa, Morell Marta, Miró Rosa, de Cid Rafael, Estivill Xavier, Casas Miquel, Bayés Mònica, Cormand Bru, Hervás Amaia
Genes and Disease Program, Center for Genomic Regulation (CRG), UPF, Barcelona, Catalonia, Spain.
Mutat Res. 2009 Jun 18;666(1-2):44-9. doi: 10.1016/j.mrfmmm.2009.03.014. Epub 2009 Apr 9.
Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric condition with onset in childhood, and in more than 50% of cases it persists into adulthood as a chronic disorder. Over five million methylphenidate (MPH) prescriptions were issued in the USA in 2003, mostly for children. A previous report [R.A. El-Zein, S.Z. Abdel-Rahman, M.J. Hay, M.S. Lopez, M.L. Bondy, D.L. Morris and M.S. Legator Cytogenetic effects in children treated with methylphenidate, Cancer Lett. 230 (2005) 284-291.] described the induction of chromosome abnormalities by MPH in children treated for three months, contrary to most of the in vitro and in vivo studies reported since then. We present new relevant information concerning the cytogenetic effects of MPH in children and adults. We include a prospective sample of 12 children and 7 adults with a new diagnosis of ADHD and naive to MPH. We analyzed the cytogenetic effects on peripheral lymphocytes before and three months after starting MPH therapy. The cytogenetic analyses included a cytokinesis-block micronucleus (CBMN) assay, a sister chromatid exchange (SCE) analysis and the determination of chromosome aberrations (CA). Following the same strategy and analyzing the same cytogenetic endpoints that were investigated in the original report [R.A. El-Zein, S.Z. Abdel-Rahman, M.J. Hay, M.S. Lopez, M.L. Bondy, D.L. Morris and M.S. Legator Cytogenetic effects in children treated with methylphenidate, Cancer Lett. 230 (2005) 284-291.], we found no evidence of increased frequency of micronuclei, sister chromatid exchanges or chromosome aberrations induced by MPH in children and adult populations. MPH treatment of children and adults with ADHD resulted in no significant genomic damage (as suggested by the three endpoints studied), results that do not support a potential increased risk of cancer after exposure to MPH.
注意力缺陷多动障碍（ADHD）是儿童期最常见的精神疾病，超过50%的病例会作为一种慢性疾病持续到成年期。2003年美国开出了超过500万份哌甲酯（MPH）处方，大部分是给儿童的。之前的一份报告[R.A. 埃尔 - 泽因、S.Z. 阿卜杜勒 - 拉赫曼、M.J. 海伊、M.S. 洛佩斯、M.L. 邦迪、D.L. 莫里斯和M.S. 莱加托 哌甲酯治疗儿童的细胞遗传学效应，《癌症快报》230（2005）284 - 291。]描述了接受三个月治疗的儿童中MPH诱导染色体异常的情况，这与自那时以来报道的大多数体外和体内研究结果相反。我们呈现了关于MPH对儿童和成人细胞遗传学效应的新的相关信息。我们纳入了12名儿童和7名成人的前瞻性样本，这些人新诊断为ADHD且未使用过MPH。我们分析了开始MPH治疗前及治疗三个月后外周淋巴细胞的细胞遗传学效应。细胞遗传学分析包括胞质分裂阻滞微核（CBMN）试验、姐妹染色单体交换（SCE）分析以及染色体畸变（CA）的测定。遵循相同的策略并分析原始报告[R.A. 埃尔 - 泽因、S.Z. 阿卜杜勒 - 拉赫曼、M.J. 海伊、M.S. 洛佩斯、M.L. 邦迪、D.L. 莫里斯和M.S. 莱加托 哌甲酯治疗儿童的细胞遗传学效应，《癌症快报》230（2005）284 - 291。]中所研究的相同细胞遗传学终点，我们未发现MPH在儿童和成人人群中诱导微核、姐妹染色单体交换或染色体畸变频率增加的证据。对患有ADHD的儿童和成人进行MPH治疗未导致显著的基因组损伤（如所研究的三个终点所示），这些结果不支持接触MPH后潜在的癌症风险增加。
