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Cyclophosphamide Boluses Induce Micronuclei Expression in Buccal Mucosa Cells of Patients with Systemic Lupus Erythematosus Independent of Cytochrome P450 2D6 Status
FRANCISCO JAVIER ACEVES AVILA, GERARDO ANTONIO ESQUIVEL NAVA, MARTHA PATRICIA GALLEGOS ARREOLA, BELINDA C. GÓMEZ MEDA, GUILLERMO M. ZÚÑIGA GONZÁLEZ, and CESAR RAMOS-REMUS
ABSTRACT.
Methods. Micronuclei (MN) assays were performed in oral mucosa sweeps of 49 patients with SLE, receiving and not receiving CYC therapy, and 43 healthy controls. In patients receiving CYC the MN assay was repeated 14 days after CYC administration. SLE patients underwent determination of the CYP2D6 allele expressed in peripheral blood by polymerase chain reaction amplification. These results were compared with CYP2D6 distribution in a healthy population from the same geographic area. The results were analyzed by Mann-Whitney U and chi-square tests. Results. Twenty-four patients with SLE received CYC boluses. The mean age of SLE patients was 32 ± 10 years; mean disease duration was 7 ± 6 years. Basal expression of MN was similar in the groups investigated and increased significantly in those exposed to CYC (CYC group 44%, no CYC group 5%, healthy controls 9%; p = 0.001). We found no association between the CYP2D6 allele expressed and MN induction. Poor metabolizers were overrepresented in SLE subjects as compared with 139 healthy controls (p < 0.05). Conclusion. Genotoxicity, as assessed by the MN assay, is increased in patients with SLE after CYC boluses. The CYP2D6 allele expressed in SLE patients does not have a role in CYC induced chromosomal injury. (J Rheumatol 2004;31:1335-9) Key Indexing Terms:
SYSTEMIC LUPUS ERYTHEMATOSUS
From the Hospital General Regional No. 46, IMSS; Departamento de Reumatología, Centro Médico Nacional de Occidente, IMSS; Unidad de Investigación en Enfermedades Crónico-Degenerativas S.C.; Laboratorio de Genética Molecular, Centro de Investigación Biomédica de Occidente, IMSS; Laboratorio de Mutagénesis, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Jalisco, México. F.J. Aceves Avila, MD, Hospital General Regional No. 46, Departamento de Reumatología, Centro Médico Nacional de Occidente; G.A. Esquivel Nava, MD, Departamento de Reumatología, Centro Médico Nacional de Occidente; M.P. Gallegos Arreola, Laboratorio de Genética Molecular, Centro de Investigación Biomédica de Occidente; B.C. Gómez Meda, MD; G.M. Zúñiga González, PhD, Laboratorio de Mutagénesis, Centro de Investigación Biomédica de Occidente; C. Ramos-Remus, MD, Departamento de Reumatología, Centro Médico Nacional de Occidente, Unidad de Investigación en Enfermedades Crónico-Degenerativas. Address reprint requests to Dr. C. Ramos-Remus, Colomos 2292, Col. Providencia, Guadalajara, Jalisco, CP 44620, México. E-mail: fjaceves@megared.net.mx Submitted June 10, 2003; revision accepted January 14, 2004. |