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

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Article · Volume 60, Issue 3 · pp. 1224–1232

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

Hongwei Liu1, Shuying Li2, Jintao Li3

  1. 1School of Medicine, University of Electronic Science and Technology of China, Chengdu, CHINA.
  2. 2School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, CHINA.
  3. 3Beijing Key Laboratory of Environmental and Viral Oncology, College of Chemistry and Life Science, Beijing University of Technology, Beijing, CHINA.

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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