Cyclophosphamide boluses induce micronuclei expression in buccal mucosa cells of patients with systemic lupus erythematosus independent of cytochrome P450 2D6 status.
OBJECTIVE
To assess the effect of cyclophosphamide (CYC) and the influence of CYP2D6 polymorphism on micronuclei expression in patients with systemic lupus erythematosus (SLE).


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).


CONCLUSIONS
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.
Aceves Avila
Francisco Javier
FJ
Hospital General Regional No. 46, IMSS; Departamento de Reumatología, Centro Médico Nacional de Occidente, Guadalajara, Jalisco, México.
Esquivel Nava
Gerardo Antonio
GA
Gallegos Arreola
Martha Patricia
MP
Gómez Meda
Belinda
B
Zúñiga González
Guillermo
G
Ramos-Remus
Cesar
C
D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000235:genetics*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D009061:Mouth Mucosa / Q000187:drug effects; D011110:Polymorphism, Genetic / Q000235:genetics
D018501:Antirheumatic Agents; D003520:Cyclophosphamide; D019389:Cytochrome P-450 CYP2D6