Folic Acid Modulates DMBA/TPA-Induced Changes in Skin of Mice: A Study Relevant to Carcinogenesis

The present study was aimed at investigating the modulatory effects of folic acid (FA) on early stages of chemically induced skin cancer. For this, a two-stage model of skin tumorigenesis was employed. 7,12-Dimethylbenz(a)anthracene (DMBA, 500 nmol/100 ul of acetone) was applied topically for two weeks (twice weekly), followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly for six weeks on the depilated skin of mice, and FA was administered orally at a dose of 40 microgram/animal for 10 weeks daily. Balb/c mice were divided into four groups depending upon the treatment they received (control, DMBA/TPA, FA, and FA+DMBA/TPA). DMBA/TPA treatment led to the formation of papillomas in DMBA/TPA and FA+DMBA/TPA groups. Ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), epidermal thickness, and cell count were evaluated to assess the beneficial effects in the early stages. FA exhibited its ameliorative potential as indicated by decreased epidermal thickness and cell count in FA+DMBA/TPA group when compared to DMBA/TPA group. Concomitantly, FA decreased the expression of ODC and PCNA in skin and activity of serum lactate dehydrogenase, suggesting inhibitory effects on cell proliferation and cell damage. Differential modulation in lipid peroxidation and reduced glutathione was observed in response to DMBA/TPA treatment and its intervention with FA. Although these findings suggest the inhibitory potential of FA during initial stages of murine skin cancer, detailed studies are warranted considering the ambiguous reports available in literature regarding the association of FA and cancer.