Comparative metabolism of benzo[a]pyrene by human keratinocytes infected with high-risk human papillomavirus types 16 and 18 as episomal or integrated genomes

Neil Trushin, Samina Alam, Karam El-Bayoumy, Jacek Krzeminski, Shantu Amin, Jenny Gullett, Craig Meyers, Bogdan Prokopczyk

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Infection with human papillomavirus (HPV) is a critical factor in the development of cervical cancer. Smoking is an additional risk factor. Tobacco smoke carcinogens, such as benzo[a]pyrene (B[a]P), and their cytochrome P450-related metabolites are present in significantly higher levels in the cervical mucus of women smokers than in nonsmokers. We determined the metabolism and P450 expression of B[a]P-treated human keratinocytes infected with HPV-16 or-18. Materials and Methods: Monolayer cultures of uninfected primary human foreskin keratinocytes, human vaginal and cervical keratinocytes carrying episomal genomes of HPV-16 and-18, respectively, and invasive cervical carcinoma cell lines carrying either HPV-16 or-18 genomes integrated into the host DNA, were incubated with 0.1 μM [3H]B[a]P. The resulting oxidative metabolites were analyzed and quantified by radioflow high-performance liquid chromatography. Additionally, all cell lines were incubated with unlabeled 0.1 μM B[a]P for Western blot analysis of cytochrome P450 1A1 and 1B1. Results: Significant enhancement in levels of both detoxification and activation metabolites was found in incubations with all types of HPV-infected cells compared with control incubations (P < 0.05). The highest capacity to metabolize B[a]P was observed with cells containing integrated HPV-18 genomes. Induction of cytochrome 1B1 was observed in HPV-16 and-18 integrated, and in HPV-16 episomal cell types. Conclusions: Both viral genotype and genomic status in the host cell affect B[a]P metabolism and cytochrome P450 1B1 expression. An increase of DNA-damaging metabolites might result from exposure of HPV-infected women to cigarette smoke carcinogens.

Original languageEnglish (US)
Article number1
JournalJournal of Carcinogenesis
Volume11
DOIs
StatePublished - Dec 1 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research
  • Health, Toxicology and Mutagenesis

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