Protective effects of vitamin c, folic acid and vitamin B12 on the mutagenic effect of methotrexate

ABSTRACT

In this study, methotrexate [MTX], a widely used anticancer drug, was tested for its potential mutagenicity in mice. An in vivo assay using two cytogenetic parameters, sister chromatid exchanges [SCEs] and chromosome aberrations [CA] in both somatic and germ cells, was done. Also, the possible protection provided by the natural antioxidant ascorbic acid [vitamin C, VC] as well as the possible scavenging properties of pteroylglutamic acid, folic acid [FA] and cyanocobalamin [vitamin B12, VB12] against the mutagenic effect of MTX were assessed. Single intraperitoneal [i.p.] treatment using 2, 5, 10, 20 mg MTX kg-1 b. wt. showed that MTX is a potent inducer of SCEs which induced a dose-dependent increase in the frequency of SCEs. The same tested doses induced an increased percentage of CA in mouse bone marrow as well as in the primary spermatocyte cells in a dose- dependent relationship. Such percentage was statistically highly significant with the two higher doses. This induction was enhanced by multiple treatments with the drug at a dose level of 10 mg kg-1 b. wt. for 4 consecutive days. For studying the possible protective effect, the mice were orally treated by gavage with VC at 50 mg kg-1 b. wt., FA at 25 mg kg-1 b. wt. and VB12 at 0.3 mg kg-1 b. wt., concurrent administration plus the repeated dose of MTX. The results revealed that CA induced with MTX was reduced to a significant extent when the treated mice received FA or VB12 but not with VC