INHIBITION OF METHOTREXATE-INDUCED CHROMOSOMAL DAMAGE BY FOLINIC ACIDIN V79 CELLS

Methotrexate (MTX), an anticancer compound, is widely used in the trea tment of leukemia. It induces cytogenetic damage as well as cytostatic effects on a variety of cell systems. Folinic acid (Leucovorin) is ge nerally administered along with MTX as a rescue agent to decrease MTX- induced toxicity. However, information regarding the inhibitory effect of folinic acid against cytogenetic damage caused by MTX is limited. This study was conducted to assess the cytogenetic effect of MTX and i ts inhibition by folinic acid (FA) using the micronucleus and chromoso mal aberration assays concurrently. Exponentially growing V79 cells we re treated with MTX at five different concentrations (5-100 mu g ml(-1 )) with Sg microsomal fraction for 6 h and post-treated with two conce ntrations of FA (5 or 50 mu g) for 40 h. Results indicate that MTX alo ne induced a concentration-related increase in % micronucleated binucl eated cells (MNBN) and % aberrant cells (Abs), There was a decrease in nuclear division index (NDI) with increase in MTX concentration. Simi larly, the mitotic index (MI) also decreased in all concentrations of MTX tested. The addition of FA at 50 mu g ml(-1) significantly reduced % MNBN (40-68%) and % Abs (36-77%). Inhibition was also seen at 5 mu g FA (12 to 54% for MNBN and 20 to 61% for Abs). These results indicat e that FA is capable of reducing the cytogenetic damage induced by MTX and appears to be an anticlastogenic agent. (C) 1998 Elsevier Science B.V.