INHIBITION OF METHOTREXATE-INDUCED CHROMOSOMAL DAMAGE BY VANILLIN ANDCHLOROPHYLLIN IN V79 CELLS

Methotrexate (MTX), a chemotherapeutic agent used to treat cancer, pro duces cytogenetic damage and has a cytostatic effect in a variety of t est systems. Several antigenotoxic agents have been studied in various in vitro and in vivo systems. However, data are limited regarding the ir ability to modulate MTX-induced genotoxicity. In the present study, vanillin (VA) and chlorophyllin (CHL) were used as antigenotoxic agen ts to study their ability to minimize the DNA damage caused by MTX. Ex ponentially growing V79 Chinese hamster lung cells were treated with M TX at five different concentrations (5-100 mu g/ml) with S9 activation for 6 h and post-treated with two concentrations of either VA (50 or 100 mu g/ml) or CHL (50 or 100 mu g/ml) for 40 h. Cytochalasin B was a dded for the micronucleus (MN) assay along with antigenotoxic agents t o evaluate MN in binucleated cells. Chromosomal aberrations were also evaluated in parallel cultures. Results indicate that MTX alone induce d a dose-dependent decrease in the nuclear division index (NDI) and th e mitotic index (MI). A significant increase in percent micronucleated binucleated cells (MNBN) and percent aberrant cells (Abs) was observe d. Studies using VA as an antigenotoxic agent showed a decrease in the number of MNBN (26.3-83.1%) and Abs (16.0-87.5%) with the addition of either 50 or 100 mu g VA/ml. The addition of CHL also significantly r educed the number of MNBN (53.0-91.5%) at both concentrations tested. Chromosomal aberrations were also significantly reduced (41.0-83.0). T hese studies indicate that both VA and CHL are capable of effectively minimizing MTX-induced chromosomal damage. (C) 1998 Wiley-Liss, Inc.