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Updated: Aug 25, 2026
Methods to Evaluate Cytotoxicity and Immunosuppression of Combustible Tobacco Product Preparations
Published on: January 10, 2015
Inhibition of experimental tobacco carcinogen induced head and neck carcinogenesis
Joel Schwartz1, Vikki Baker, Eric Larios
1American Health Foundation, Molecular Pathology Facility, Institute for Cancer Prevention, One Dana Road, Valhalla, NY 10595, USA. jls3643@aol.com
Abstract:
Oral cancer models have attempted to demonstrate inhibition of oral carcinogenesis. These models used synthetic carcinogens, lacked a specific mechanism of activity or used non-physiologic doses for carcinogen or inhibitor. To correct these problems the tobacco and environmental carcinogen, dibenzo[a,l]pyrene (DB[a,l]P) (0.25%, 0.010 microM/application) was painted on the tongue and/or vitamin E acid succinate (VE(as)) (0.43 I.U./0.136 (microM/treatment) administered by gavages to Syrian hamsters (14 animals per group) using physiologic low doses, 5X/week. Oral cytology supplied keratinocytes after 1, 10, or 25 weeks of treatment. Cells were analyzed by flow cytometry/laser scanning cytometry. Initiation (1-6 weeks) was suppressed by reducing DNA damage (oxidation lesions: 8-oxo-dG), and repair (comet, fpg, OGG1, NTH1). Reduction in promotion (6-10 weeks) was identified by depressed proliferation (cell cycle, bromodeoxyuridine incorporation (BrdU)) and aneuploidy (propidium iodide stain). p53 and apoptosis expressions were increased (Sub G(1), mitochondrion activation: Apo 2.7, and nucleosomal formation: mebstain (TUNEL)). VE(as) administration reduced dysplasia (10 weeks) and oral cancer formation at 25 (0/7 vs. 5/7 DB[a,l]P) and 30 weeks (3/7 vs. 6/7 DB[a,l]P). Inhibition of oral carcinogenesis by VE(as) involved reversal of several cellular events that contribute towards oral cancer.
Insights
Vitamin E succinate (VE(as)) effectively inhibited oral carcinogenesis in hamsters by reducing DNA damage and cell proliferation. This study provides a more accurate model for testing oral cancer inhibitors.
Area of Science:
- Oncology
- Carcinogenesis Research
- Preventive Medicine
Background:
- Existing oral cancer models often use non-physiologic doses of carcinogens or inhibitors.
- There is a need for more accurate models that mimic human exposure to carcinogens and test potential inhibitors effectively.
Purpose of the Study:
- To establish a more accurate oral cancer model using a specific carcinogen and evaluate the inhibitory effects of vitamin E succinate (VE(as)).
- To investigate the cellular mechanisms by which VE(as) inhibits oral carcinogenesis.
Main Methods:
- Syrian hamsters were treated with dibenzo[a,l]pyrene (DB[a,l]P) and/or VE(as) at low, physiologic doses.
- Oral keratinocytes were analyzed using flow cytometry and laser scanning cytometry at various time points.
- Key markers for DNA damage, repair, proliferation, aneuploidy, p53 expression, and apoptosis were assessed.
Main Results:
- VE(as) suppressed oral carcinogenesis initiation by reducing DNA oxidation lesions (8-oxo-dG) and enhancing DNA repair.
- Promotion was inhibited by decreased cell proliferation and aneuploidy.
- VE(as) increased p53 expression and apoptosis, reduced dysplasia, and significantly decreased oral cancer formation at 25 and 30 weeks.
Conclusions:
- VE(as) demonstrates significant potential in inhibiting oral carcinogenesis through multiple cellular mechanisms.
- This study validates a more precise animal model for oral cancer research using low-dose carcinogen exposure.
- The findings suggest VE(as) could be a promising agent for the prevention of oral cancer.
