Oral Cavity Carcinogenesis Modeled in 4NQO Treated Mice

Methods: 0.001% and 0.002% 4NQO in drinking water was administered orally to Balb/c mouse for 16-28 weeks. Then the mice were killed and their tongues were removed for histological assessment.

Results: After treatment with 4-NQO in the drinking water, gross and microscopic changes have been found on the tongue of the mouse. Gross changes included white changes, leukoplakia and erythroplakia appearances and verrucous hyperplasia on the posterior mucosa of the tongue dorsum of experimental group mice during carcinogenesis. Their corresponding histopathological results ranged from hyperplasia, mild dysplasia (MiDP), moderate dysplasia (MoDP), severe dysplasia (SDP), in situ carcinoma(ISC) to early invasive carcinoma(EIC). The tongues of mice treated with 0.001% 4NQO for 16 weeks showed MiDP (50.0%), MoDP (45.0%) and SDP (5.0%); the tongues of mice treated with 0.001% 4NQO for 20 weeks showed MiDP (5.0%), MoDP (60.0%), SDP (30.0%), ISC (5.0%); the tongues of mice treated with 4NQO for 24 weeks showed MoDP (50.0%), SDP (40.0%), ISC (10.0%). The incidence of tongue cancer in mice treated with 0.002% 4NQO for 16 weeks, 20 weeks, 24 weeks, 28 weeks and then observed for 40 weeks was 10%, 25%, 37.5% and 45.5% respectively. No metastases were found.

Conclusions: 4NQO can reliably induce mouse tongue preneoplastic lesions, carcinoma of the mouse tongue mucosa. The process of carcinogenesis and the biological behavior parallel those of human oral carcinoma. The target organ is typical, the method is handy. 0.001% is the best concentration to induce the mouse model of occurrence and 0.002% is the best concentration to induce the mouse model of tongue epithelial carcinoma.