Reference SummaryHendler FJ, 1996;():79-87


4-nitroquinoline-1-oxide (4NQO)-induced murine oral cavity carcinogenesis: A paradigm of human head and neck cancer.


Hendler FJ; Yuan B; Heniford BW; Hawkins BL; Oechsli MN; Lentsch EM; Hu LH; Menes JC; Alagar R; ShumSiu A; Ackermann DM









Background. To study the molecular events involved in human squamous cell neoplastic transformation, we have established an in vivo murine model treating oral epithelium with 4-nitroquinoline-1-oxide (4NQO), a complete carcinogen. 4NQO causes DNA adducts which results in specific G to A transitions. Methods. 4NQO was applied to the mouse oral epithelium for 4 to 16 weeks. Tumors that developed were evaluated for H. Ras mutations, loss of heterozygosity (LOH), gene amplification, and genomic instability. Results. Oral cavity squamous cell carcinomas (HNSCC) developed which resembled human tumors. The tumors molecularly resemble HNSCC with 60% of mice developing H. Ras mutations at codon 12. Half of the tumors with ras mutation developed LOH on chromosome (Chr) 7. P53 mutations are present in 75% of tumors. Those tumors with LOH developed gene amplification and genomic instability. Discussion. The morphology and the molecular events demonstrate that 4NQO-induced tumors resemble human HNSCC particularly that developing among tobacco chewers from India and the US. Thus, 4NQO-induced tumorigenesis is an excellent model to explore oral cavity carcinogenesis and the molecular pathways involved in neoplastic transformation.


J:39261 – MGI References


Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
CBA/J Oral cavity squamous cell carcinoma
  • 4-nitroquinoline-1-oxide (4NQO)
Oral cavity

very high