Inhibition of experimental tobacco carcinogen induced head and neck carcinogenesis.
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.
Schwartz
Joel
J
American Health Foundation, Molecular Pathology Facility, Institute for Cancer Prevention, One Dana Road, Valhalla, NY 10595, USA. jls3643@aol.com
Baker
Vikki
V
Larios
Eric
E
Desai
Dhimant
D
Amin
Shantu
S
D000782:Aneuploidy; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001580:Benzopyrenes; D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D006224:Cricetinae; D004260:DNA Repair / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics; D004195:Disease Models, Animal; D006868:Hydrolysis; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D008647:Mesocricetus; D048629:Micronuclei, Chromosome-Defective; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001580:Benzopyrenes; D004273:DNA, Neoplasm; D014810:Vitamin E; C041517:dibenzo(a,l)pyrene; D024505:Tocopherols