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Alcohol Metabolism by Oral Streptococci and Interaction with Human Papillomavirus Leads to Malignant Transformation of Oral Keratinocytes

  • Lin Tao
  • Sylvia I. Pavlova
  • Stephen R. Gasparovich
  • Ling Jin
  • Joel Schwartz
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 815)

Abstract

Poor oral hygiene, ethanol consumption, and human papillomavirus (HPV) are associated with oral and esophageal cancers. However, the mechanism is not fully known. This study examines alcohol metabolism in Streptococcus and its interaction with HPV-16 in the malignant transformation of oral keratinocytes. The acetaldehyde-producing strain Streptococcus gordonii V2016 was analyzed for adh genes and activities of alcohol and aldehyde dehydrogenases. Streptococcus attachment to immortalized HPV-16 infected human oral keratinocytes, HOK (HPV/HOK-16B), human oral buccal keratinocytes, and foreskin keratinocytes was studied. Acetaldehyde, malondialdehyde, DNA damage, and abnormal proliferation among keratinocytes were also quantified. We found that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB, and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol, and ethanol, respectively. S. gordonii V2016 did not show a detectable aldehyde dehydrogenase. AdhE is the major alcohol dehydrogenase in S. gordonii. Acetaldehyde and malondialdehyde production from permissible Streptococcus species significantly increased the bacterial attachment to keratinocytes, which was associated with an enhanced expression of furin to facilitate HPV infection and several malignant phenotypes including acetaldehyde adduct formation, abnormal proliferation, and enhanced migration through integrin-coated basement membrane by HPV-infected oral keratinocytes. Therefore, expression of multiple alcohol dehydrogenases with no functional aldehyde dehydrogenase contributes to excessive production of acetaldehyde from ethanol by oral streptococci. Oral Streptococcus species and HPV may cooperate to transform oral keratinocytes after ethanol exposure. These results suggest a significant clinical interaction, but further validation is warranted.

Keywords

Alcohol Ethanol Acetaldehyde Dehydrogenase ADH ALDH Cancer Carcinogenesis Keratinocytes Human papillomavirus HPV Streptococcus 

Notes

Acknowledgements

This work was supported by a grant from NIH National Cancer Institute (CA162537). We thank Dr. Mark Herzberg for sending us 14 oral Streptococcus laboratory strains. We thank Drs. Antonia Kolokythas, Mulokozi Lugakingira, and Michael Miloro for collecting human oral buccal keratinocytes and other technical assistance.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Lin Tao
    • 1
  • Sylvia I. Pavlova
    • 1
  • Stephen R. Gasparovich
    • 2
  • Ling Jin
    • 1
  • Joel Schwartz
    • 3
  1. 1.Department of Oral BiologyCollege of Dentistry, University of Illinois at ChicagoChicagoUSA
  2. 2.BiloxiUSA
  3. 3.Department of Oral Medicine and Diagnostic Sciences, College of DentistryUniversity of Illinois at ChicagoChicagoUSA

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