A Mouse Model Of Tongue Epithelial Carcinoma Induced By 4-nitroquinolinel-oxide (4NQO) In Drinking Water

Objective: To examine the influence of water-soluble carcinogen 4NQO on the oral mucosa squamous epithelium of Balb/c mice, with the specific objective of determining the carcinogenicity of 4NQO, we want to establish a mouse model of tongue epithelial carcinoma which is easy to establish repeatedly and similar with human oral squamous cell carcinoma. Materials and methods : Chemical carcinogen 4-nitroquinoline 1-oxide (4NQO) (Sigma Chemical CO.) in drinking water was administered to 120 Balb/c mice of experimental group. Water was administered to 30 Balb/c mice of control group. The experimental group was divided into 2 subgroups, team A and team B. Team A was divided into four subgroups A1, A2, A3, A4, which contained 20, 20, 10, 10 mice and received application of 4NQO solution for 16, 20, 24, 28 weeks, respectively. The mice of team A were killed at 16, 20, 24, 28 weeks respectively. Team B was divided into four subgroups B1, B2, B3, B4, which contained 10, 10, 15, 25 mice and received application of 4NQO for 16, 20, 24, 28 weeks, then received application of water until 48 weeks, respectively. All the mice of team B were killed at 48 weeks. Five mice of control group were killed at 16, 20, 24, 28 weeks, respectively. The rest mice of control group were killed at 48 weeks. When the experiment was terminated and specimens were taken for histological assessment. The data was analyzed statistically. Results: 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. The severity of the lesion corresponded to the duration of treatment and length of observation. 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 mice of A1 subgroup showed MiDP (50.0%), MoDP(45.0%) and SDP (5.0%); the mice of A2 subgroup showed MiDP (5.0%), MoDP(60.0%), SDP(30.0%), ISC(5.0%); the mice of A3 subgroup showed MoDP(50.0%), SDP(40.0%), ISC(10.0%); the mice of A4 subgroup showed MoDP(30.0%), SDP(50.0%), ISC(10.0%), EIC(10.0%). The mice of B1 subgroup showed MoDP(40.0%), SDP(60.0%); the mice of B2 subgroup showed MoDP(14.3%), SDP(71.4%), ISC(14.3%); the mice of B3 subgroup showed MoDP(18.2%), SDP(63.6%), ISC(9.1%), EIC(9.1%); the mice of B4 subgroup showed MoDP(20.0%), SDP(52.0%), ISC(16.0%), EIC(12.0%). Conclusions: 1.4NQO can reliably induce mouse tongue preneoplastic lesions, which morphologically and histologically mimic human oral preneoplastic lesions. 2. 4NQO also can induce mouse tongue epithelial carcinoma, the carcinogenesis experiences from the prenoeplatic lesion to carcinoma slowly. The target organ is typical, the histopathological character is similar with human oral squamous epithelial carcinoma. But the rate of tongue epithelial carcinoma is not high. 3. The method of soluble-carcinogen 4NQO in drinking water can induce the preneoplastic lesion and carcinoma of the mouse tongue mucosa reliably, which is natural and handy. The process of carcinogenesis and the biological behavior parallel those of human oral carcinoma. 4. 4～5months application of 0.001% 4NQO is the best period to preneoplastic induction. If we want to induce the tongue epithelial carcinoma in the prescriptivetime with higher rate, we should increase the concentration of the 4NQO.