In vitro and animal studies of the role of viruses in oral carcinogenesis.
The linkage of herpes simplex virus (HSV) and human papillomavirus (HPV) to the development of oral cancer has been studied. In spite of the presence of viral nucleic acids in some human oral cancer specimens, HSV alone is not carcinogenic in animals: repeated viral inoculation to mouse or hamster oral mucosa fails to produce tumours or histopathological evidence of malignancy. However, HSV demonstrates co-carcinogenicity in vivo: viral inoculation significantly enhances the oncogenic capacity of chemical carcinogens in the oral cavity of mice and hamsters. Though the detailed mechanisms of HSV cocarcinogenicity are unknown, HSV promotes the chemical carcinogen-induced activation of certain cellular proto-oncogenes and inactivation of p53 tumour suppressor gene. Human papillomaviruses type 16 (HPV-16) and 18 (HPV-18) demonstrate oncogenicity by transforming normal human oral keratinocytes in vitro. While normal cells exhibit a limited life-span, cells transformed by these viruses show immortality and altered morphology in comparison with their normal counterparts. The HPV-immortalised cells contain multiple copies of intact viral genome integrated into cellular chromosomes. These cells also express several viral-specific mRNAs including viral E6/E7 mRNAs. Notably, these cells contain low levels of p53 protein and overexpressed cellular myc proto-oncogene compared to their normal counterpart; however, the immortilised cell lines are non-tumorigenic in nude mice.
Park
N H
NH
UCLA School of Dentistry, Los Angeles, California.
Li
S L
SL
Xie
J F
JF
Cherrick
H M
HM
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D015197:Carcinogenicity Tests; D003043:Cocarcinogenesis; D006224:Cricetinae; D004279:DNA, Viral / Q000032:analysis; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000382:microbiology*; D009857:Oncogenes; D027383:Papillomaviridae / Q000472:pathogenicity*; D000090063:Proto-Oncogene Mas; D018139:Simplexvirus / Q000472:pathogenicity*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014412:Tumor Virus Infections
D004279:DNA, Viral; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene