title: Impaired nucleotide excision repair in UV-irradiated human oral keratinocytes immortalized with type 16 human papillomavirus genome.
abstract: We previously reported that 'high risk' human papillomaviruses (HPV) induce genetic instability in human oral keratinocytes. To understand the mechanisms of HPV-induced genetic instability, we determined the nucleotide excision repair (NER) capacity of normal (NHOK) and human papillomavirus type-16 immortalized oral keratinocytes (HOK-16B) by strand-specific removal of UV-induced cyclobutane pyrimidine dimers (CPDs) from a 16 Kb fragment of the p53 gene. In NHOK the NER activity was initiated in both DNA strands immediately, although the process in the non-transcribed strand was notably slower than that of the transcribed strand. In HOK-16B cells the initiation of CPDs removal was delayed for at least 8 h in both DNA strands, and the process was significantly slower than that in NHOK. UV-irradiation enhanced the p53 protein level more than 30-fold in NHOK, but it did not significantly alter the protein level in the HOK-16B cells. UV-irradiation also increased the p21WAF1/CIP1 protein level only in NHOK. These data indicate that 'high risk' HPV induces genetic instability by impairing NER capacity of cells. Impaired NER activity of HOK-16B cells may be implicated with their inability to enhance active p53 when challenged by genotoxic stress.
authors.affiliation: UCLA School of Dentistry 90095-1668, USA.
authors.forename: O
authors.initials: O
authors.lastname: Rey
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: N H
authors.initials: NH
authors.lastname: Park
mesh_terms: D002461:Cell Line, Transformed; D004260:DNA Repair; D016158:Genes, p53; D016679:Genome, Viral; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects* / Q000821:virology; D009061:Mouth Mucosa / Q000378:metabolism / Q000528:radiation effects / Q000821:virology; D018384:Oxidative Stress; D027383:Papillomaviridae / Q000235:genetics*; D014466:Ultraviolet Rays