ab2002

Genotoxicity assessment using micronuclei assay in rheumatoid arthritis patients

C. Ramos-Remus^1,3, G. Dorazco-Barragan¹, F.J. Aceves-Avila¹, F. Alcaraz-Lopez¹, F. Fuentes-Ramirez¹, J. Michel-Diaz¹, O. Torres-Bugarin², A. Ventura-Aguilar², G. Zuñiga-González²

¹Department of Rheumatology and the ²Department of Mutagenesis, Centro Mèdico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Mexico, and the ³Unidad de Investigacion en Enfermedades Crónico-Degenerativas, S.C. Guadalajara, Mexico.

ABSTRACT
Objectives
This study investigated whether: (i) rheumatoid arthritis (RA) patients have more micronuclei (MN) than healthy controls; (ii) methotrexate (MTX) treated RA patients have more MN than those not using MTX, and (iii) folic acid supplementation decreases the number of MN in MTX treated patients.

Methods
MN assays were performed in oral mucosa sweeps of 50 consecutive MTX treated RA patients, 30 consecutive RA patients not receiving MTX and 39 healthy controls. MTX treated RA patients were then randomly placed in a cross-over design to receive folic acid supplementation, and MN assays were repeated after 6 weeks.

Results
The MTX-RA patients had a mean age of 46 ± 10 yrs and a mean disease duration of 12 ± 9 yrs; 80% were women. The MTX dose range was 8.7 ± 1.5 mg/week and the mean duration of use was 16 ± 18 months. In the non-MTX RA group, the mean age was 48 ± 14 yrs, the mean disease duration was 13 ± 9 yrs, and 87% were women. At baseline, the number of MN were significantly higher in RA patients as compared with controls (3.31 ± 2.3 vs 0.8 ± 0.8, p < 0.001). No difference in MN numbers was observed between users and non-users of MTX. Folic acid supplementation did not decrease the MN number in the MTX treated RA patients.

Conclusions
Genotoxicity, as assessed by the MN assay, is increased in RA patients. These results suggest that genotoxicity is associated with RA itself and not with MTX use. Folic acid supplementation had no effect on the number of MN.

Key words
Micronuclei, rheumatoid arthritis, methotrexate.

Supported by Fondo de Fomento a la Investigación grant No. FP 0038/859 of
the Instituto Mexicano del Seguro Social.
Please address correspondence to: Dr. Cesar Ramos Remus, Colomos No. 2292, Providencia, Guadalajara, Jal. 44620 Mexico.
E-mail: rramos@udgserv.cencar.udg.mx