Inhibition of methotrexate-induced chromosomal damage by vanillin and chlorophyllin in V79 cells.
Keshava-C; Keshava-N; Whong-WZ; Nath-J; Ong-TM
Teratog, Carcinog, Mutagen 1997 Jan; 17(6):313-326
Methotrexate (MTX), a chemotherapeutic agent used to treat cancer, produces cytogenetic damage and has a cytostatic effect in a variety of test systems. Several antigenotoxic agents have been studied in various in vitro and in vivo systems. However, data are limited regarding their ability to modulate MTX-induced genotoxicity. In the present study, vanillin (VA) and chlorophyllin (CHL) were used as antigenotoxic agents to study their ability to minimize the DNA damage caused by MTX. Exponentially growing V79 Chinese hamster lung cells were treated with MTX at five different concentrations (5-100 g/ml) with S9 activation for 6 h and post-treated with two concentrations of either VA (50 or 100 g/ml) or CHL (50 or 100 g/ml) for 40 h. Cytochalasin B was added for the micronucleus (MN) assay along with antigenotoxic agents to evaluate MN in binucleated cells. Chromosomal aberrations were also evaluated in parallel cultures. Results indicate that MTX alone induced a dose-dependent decrease in the nuclear division index (NDI) and the mitotic index (MI). A significant increase in percent micronucleated binucleated cells (MNBN) and percent aberrant cells (Abs) was observed. 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 g VA/ml. The addition of CHL also significantly reduced the number of MNBN (53.0-91.5%) at both concentrations tested. Chromosomal aberrations were also significantly reduced (41.0-83.0). These studies indicate that both VA and CHL are capable of effectively minimizing MTX-induced chromosomal damage.
Cancer; Toxins; Toxic-effects; Cellular-structures; Cellular-reactions; Cellular-function; Cellular-uptake; Cell-transformation; In-vivo-studies; In-vitro-studies; Chromosome-damage; Chromosome-disorders
Tong-man Ong, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505-2845
Teratogenesis, Carcinogenesis, and Mutagenesis