Inhibition of experimental tobacco carcinogen induced head and neck carcinogenesis.

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.

• Authors: Joel Schwartz, Vikki Baker, Eric Larios, Dhimant Desai, Shantu Amin
• Journal: Oral oncology (Oral Oncol) Vol. 40 Issue 6 Pg. 611-23 (Jul 2004) ISSN: 1368-8375 [Print] England
• PMID: 15063390 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Benzopyrenes
• DNA, Neoplasm
• Vitamin E
• dibenzo(a,l)pyrene
• Tocopherols

Topics

• Aneuploidy
• Animals
• Antineoplastic Agents (metabolism, therapeutic use)
• Apoptosis (drug effects)
• Benzopyrenes
• Cell Cycle (drug effects)
• Cell Transformation, Neoplastic (chemically induced, genetics, pathology)
• Cricetinae
• DNA Repair (drug effects)
• DNA, Neoplasm (genetics)
• Disease Models, Animal
• Hydrolysis
• Keratinocytes (drug effects, pathology)
• Mesocricetus
• Micronuclei, Chromosome-Defective
• Mouth Neoplasms (chemically induced, pathology, prevention & control)
• Tocopherols
• Vitamin E (analogs & derivatives, metabolism, therapeutic use)