Assessment of Cytotoxicity and Genotoxicity in Patients with Rheumatoid Arthritis and its Relation to Disease Activity and Medications

Objectives: To assess the chromosomal aberrations (CAs) as a measure of cytotoxicity and micronuclei (MNi) and
nucleoplasmic bridges (NPB) as a measure of genotoxicity in patients with rheumatoid arthritis (RA) and its relation to the
disease activity. The work also aimed to assess the possible cytotoxicity and genotoxicity induced by some Disease
Modifying Anti-Rheumatic Drugs (DMARDs) used for treatment of RA patients. Patients and Methods: The study included
20 female RA patients treated with DMARDs (MTX and SSZ), 10 RA patients not receiving DMARDs (used NDAIDs), and
10 control. Peripheral blood samples were taken to assess the cytotoxicity by chromosomal analysis (karyotyping) using solid Giemsa stain and GTG- banding according to the International System for Human Chromosome Nomenclature. Genotoxicity and DNA damage was assessed by the miconucleus (MN) test using cytochalasin-B. Results: The DMARDs RA patients had a mean age of 42.2±11.76 yr and a mean disease duration of 7.95±6.43 yr. The MTX dose was 50 mg/wk and the SSZ dose was 500 mg/ 8 hours, and the mean duration of use was 7.1±6.27 yr. The 20 RA patients of the DMARDs group received folic acid dose of 0.5 mg/day for the same period as DMARDs. The mean age of the non- MTX RA (NSAIDs) group was 43.1±13.5 yr, the mean disease duration was 4.3±1.9 yr. The results showed a high significant increase (p<0.001) of chromosomal breaks, satellite association, chromosome endoreduplication, aneuploidy, and other CAs in RA patients compared to control. This significant difference was not correlated with disease activity. Cytotoxicity of MTX was illustrated by the significant increase in the number of satellite association, and cells with aneuploidy when compared to the NSAIDs group. The frequency of micronuclei (MNi), nucleoplasmic bridges (NPB), and necrotic and/or apoptotic cells were significantly higher in RA patients when compared to control (p<0.05) but not correlated to disease activity. RA patients receiving DMARDs showed a significant increase in the number of binucleated cells with one MN when compared to the NSAIDs group. Conclusion: CAs, MNi, and NPB were increased RA patients so suggesting that cytotoxicity and genotoxicity are manifestations of RA disease itself. These CAs, MNi, and NPB were not correlated to the degree of disease activity, and seemed to be randomly distributed except in the case of X- chromosome anomalies. MTX is still cyto-and genotoxic to RA patients despite the associated use of folic acid. This toxicity might be due to the high dose and its long time of use in the present study. [Egypt J Rheumatology & Clinical Immunology, 2016; 4(1): 67-80]