Abstract
The objective of this study was to determine the effects of hydrogen peroxide alone and in combination with 7,12-dimethylbenza[a]anthracene (DMBA) in the oral cavity because H2o2, has been implicated as a complete carcinogen or cocarcinogen in two animal models. In the two independent studies, golden Syrian hamsters were used to evaluate the carcinogenic and cocarcinogenic potential of dentifrices containing H2o2 and NaHCO3. In the first study, the cocarcinogenic potential of a dentifrice containing 0.75% H2O2/ 5% baking soda was compared with that of a commercial dentifrice with similar ingredients except baking soda and H2O2. In the second study, the cocarcinogenic potential of a dentifrice formulated with 1.5% H, sb>2O2/7.5% baking soda was compared with a mixture of 3% H2O2/baking soda. All materials were applied to the right cheek pouches of experimental animals, and the left cheek pouches were untreated. In the first study. 0.5% DMBA was administered five times weekly for 20 weeks, and the dentifrices were applied immediately after the DMBA. Dentifrices or mineral oil alone were also applied five times weekly. In the second study. 0.5% DMBA or 0.25% DMBA were applied three times weekly for 16 weeks; dentifrices (or 3% H2O2/baking soda) were applied five times weekly for 16 weeks. The dual-phase dentifrice containing 0.75% H2O2/5% baking soda was not carcinogenic, and in combination with DMBA resulted in no observable acceleration of tumor onset, compared with DMBA alone. In fact, animals treated with 0.5% DMBA and the H2O2/baking soda dentifrice had a significantly delayed onset of tumor formation than did animals treated with DMBA alone. In the second bioassay, an increased latency period for tumor formation was observed with 0.5% DMBA and a dual-phase dentifrice containing 1.5% H2O2/7.5% baking soda, compared with 0.5% DMBA alone. With 0.25% DMBA, latency was not affected by addition of the dual-phase dentifrice. In contrast, animals receiving 0.25% DMBA and 3% H2O2/ NaHCO3 had a significantly lower rate of tumor formation and overall mass incidence. Croton oil also reduced the rate of tumor formation when applied with 0.25% DMBA. Histopathologic examination of cheek pouches revealed squamous cell carcinomas in the majority of DMBA-treated animals. Cheek pouches of DMBA-treated animals killed at interim times indicated a progression from keratotic changes and/or dyskeratosis at 6 weeks with the occurrence of carcinomas in approximately half the animals examined at 12 weeks. No significant histopathologic abnormalities were observed in animals not receiving DMB A other than slight keratosis in the oral mucosa of one or two animals per group. These results demonstrated that an oral product containing baking soda and hydrogen peroxide was not carcinogenic, and that baking soda and H2O2 did not enhance the tumorigenicity of DMB A. Furthermore, the tumor-igenic response of DMBA was reduced by coadministration of 3% H2O2 and sodium bicarbonate.