Mutations in the hypoxanthine phosphoribosyltransferase (hprt) gene in T lymphocytes from arthritis patients and in human B lymphoid cell lines exposed to nitric oxide-donating drugs.

Abstract

There is evidence that nitric oxide (NO), a reactive free radical produced in large quantities by resident synoviocytes, chondrocytes and infiltrating macrophages, is elevated in the synovial fluid and serum of rheumatoid arthritis (RA) patients. Observations within our lab suggest that NO may be capable of causing mutations of significant size, including large-scale deletion (LSD) mutations. Since NO has been shown to cause DNA damage and since genetic changes also occur in the inflamed joints, we hypothesize that NO may participate in the genotoxic environment of RA joints. To determine if LSD mutations contribute to the increase in T cell hprt MF observed earlier, hprt mutant ( hprt-) T cells were isolated from RA patients and screened by multiplex-PCR (MP-PCR) for deletion of hprt exons. To determine if NO is capable of inducing LSD mutations such as those found in RA and OA T cells, two human B lymphoblastoid cell lines (TK6 and WIL2-NS) were exposed to NO-donating drugs and the resulting hprt - clones were examined for hprt LSD mutations by MP-PCR. (Abstract shortened by UMI.)