Neil Christensen (United States of America)

Pennsylvania State University College of Medicine Pathology Department, C7800

Presenter of 1 Presentation

 Conference Calendar
Basic Research / Animal Models ePoster

DIBENZO[A,L]PYRENE (DB[A,L]P), A TOBACCO ORAL CARCINOGEN, IS A CO-FACTOR FOR MALIGNANT PROGRESSION OF MOUSE ORAL PAPILLOMAVIRUS INFECTIONS. (ID 843)

Session Date
07/21/2020
Session Time
10:00 - 17:00
Room
ePoster
Session Type
Poster Viewing - 20-24 July
Session Name
Basic Research / Animal Models
Lecture Time
10:00 - 10:01
Presenter
Authors

Abstract

Introduction

We have established a mouse papillomavirus (MmuPV1) model to test the role of various co-factors in oral HPV-associated disease progression. Select tobacco carcinogens were applied orally and daily for 10 weeks starting 4 weeks after oral MmuPV-1 infection of athymic mice. The purpose of the study was to ascertain whether the co-presence of oral tobacco carcinogens could accelerate oral PV disease progression.

Methods

Groups of athymic mice of both genders were infected with MmuPV1 in the oral cavity using our delayed-wounding infection model. The experiment included 4 cohorts of mice that were treated orally: (1) infected with MmuPV1 and treated with DMSO-saline; (2) infected with MmuPV1 and treated with the tobacco carcinogen dibenzo[a,l]pyrene (DB[a,l]P) (DBP); (3) uninfected and treated with DMSO-saline, and (4) uninfected and treated with DBP. At 4 weeks after virus infection, oral treatments began and continued for 10 additional weeks. At monthly intervals, oral lavages were collected for subsequent assessment of viral load via qPCR. At 14 weeks post viral infection, the experiment was terminated, and mouse oral tissues were collected for histology (H&E), in situ hybridization for viral DNA, immunohistochemistry for viral capsid protein, and pathological assessment for papillomatous morphology and appearance of squamous cell carcinoma in situ.

Results

We observed increased rates of squamous cell carcinoma (SCC) in situ in oral tissue infected with MmuPV1 and treated orally with DBP. Mice treated with DBP alone showed minimal disease. Virally-infected epithelium showed strong levels of viral DNA and capsid protein staining whereas areas of SCC showed reduced viral DNA staining indicative of lower viral copy per nucleus that correlates with HPV cancers.

Conclusions

We have confirmed that the mouse oral PV infection model is an excellent platform to assess the impact of co-factors such as tobacco carcinogens for oral PV cancerous progression.

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