Inhibition of oral carcinogenesis by glutathione

Forty young adult Syrian hamsters (Mesocricetus auratus) were divided into four groups of 10 animals each. In Group 1 (tumor control), the right buccal pouches were painted three times per week with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in heavy mineral oil (USP) with a no. 4 sable brush. In Group 2 (experimental group), the right buccal pouches were painted with DMBA, as in Group 1. In addition, Group 2 received 1 mg of reduced glutathione in 0.5 ml of mineral oil three times per week on days alternate to the DMBA application. The glutathione was administered systemically by mouth with a pipette. Group 3 received only glutathione, and Group 4 was untreated (control groups). Animals were sacrificed after 14 weeks, and tumors were counted and measured. Both right and left pouches were photographed, excised, fixed in formalin, sectioned in paraffin, and studied histologically. The animals receiving glutathione demonstrated significantly fewer and smaller tumors. The mean tumor burden was 315 mm3 in the glutathione-treated group and 3,040 mm3 in the untreated group. The statistical significance by Student's t test was < or = 0.0001. Histological study also revealed significantly fewer areas of dysplastic leukoplakia in the group treated with glutathione. This study represents the first demonstration of the anticancer effect of systemically administered reduced glutathione.