Genotoxicity assessment using micronuclei assay in rheumatoid arthritis patients.
OBJECTIVE
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.
Ramos-Remus
C
C
Department of Rheumatology, Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara. rramos@udgserv.cencar.udg.mx
Dorazco-Barragan
G
G
Aceves-Avila
F J
FJ
Alcaraz-Lopez
F
F
Fuentes-Ramirez
F
F
Michel-Diaz
J
J
Torres-Bugarin
O
O
Ventura-Aguilar
A
A
Zuñiga-González
G
G
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics*; D019457:Chromosome Breakage; D005260:Female; D005492:Folic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D008875:Middle Aged
D018501:Antirheumatic Agents; D005492:Folic Acid; D008727:Methotrexate