A Glimpse of the Interaction between N-Nitrosamines and HPV E5 in Rodent Cell Transformation

Indian Journal of Pharmaceutical Education and Research

  • Hongwei Liu1School of Medicine, University of Electronic Science and Technology of China, Chengdu, CHINA.
  • Shuying Li2School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, CHINA.
  • Jintao Li3Beijing Key Laboratory of Environmental and Viral Oncology, College of Chemistry and Life Science, Beijing University of Technology, Beijing, CHINA.

Volume 60 Issue 3 Pages 1224-1232

DOI: 10.5530/ijper.20263287

Abstract

Background: A few epidemiologic surveys and experimental studies observed the synergistic carcinogenic effect of nitrosamines and High-Risk Human Papillomavirus (HPV) in partial digestive tract cancers. They mainly focused on the co-carcinogenesis of HPV E6 and E7 in cancer development. HPV E5 plays an important role in early-stage cancer but has limited capacity as an independent carcinogen. Objective: To investigate whether nitrosamines enhance the carcinogenesis of E5, a rapid in vitro rodent cell transformation assay was established. Materials and Methods: We have successfully established BALB/c 3T3-E5 cells expressing HPV16 E5 using a lentivirus vector. Six foodborne N-nitroso Compounds (NOCs) are selected to induce malignant cell transformation. Results: We have screened two compounds with strong transformation capability, N-nitrosodimethylamine and N-nitrosodiethylamine alone. The combined action of NOCs and E5 is highly efficient, with more transformed foci than a single NOC or E5 oncoprotein, and the synergistic effect becomes more evident with increasing concentrations of NOCs, especially N-nitrosodipropylamine. Furthermore, we also confirm the working concentration range of 0.05-0.1 ng/mL of NOCs to meet the demands for cell viability in carcinogenicity tests. Conclusion: In conclusion, we provide cell models for studying the interaction mechanism of HPV16 E5 and NOCs, as well as assessing preventive or therapeutic candidates for HPV-positive tumors in the future.

Keywords

  • Human Papillomavirus16
  • E5 oncoprotein
  • N-nitrosamines
  • BALB/c 3T3 cell
  • Synergy
  • effect
  • Carcinogenicity
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