The toxicity of folic acid (PGA) was studied in different inbred strains of mice. LD50 values of PGA by the i.p. route showed a unique toxicity pattern. In some strains, convulsions, ataxia and weakness were observed. Histopathological study in strains S/RVCri, BDF1, DBA/2 and DBA/2fNCri showed acute renal tubular necrosis.
Folic acid (FA) was combined with anticancer agents such as (i) antimetabolites like methotrexate (MTX), 5-fluorouracil (5-FU), arabinosyl cytosine (Ara-C) and 6-mercaptopurine (6-MP); (ii) plant-derived mitotic inhibitor, vincristine (VCR), and (iii) an antibiotic, mitomycin C (Mit-C). This combination modality was used for the treatment of P388 lymphocytic leukaemia. Large doses of FA were administered to the tumour-bearing mice either prior to or simultaneously with different anticancer agents. Pre-treatment with FA significantly improved the therapeutic efficacy of 5-FU, Ara-C and Mit-C; while MTX was more effective when given simultaneously with FA. The efficacy of 6-MP and VCR was not enhanced by FA when tested similarly. Large doses of FA can potentiate the activity of certain anticancer agents when administered to P388-bearing mice at critical times that vary according to the particular drug used.
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