Impaired nucleotide excision repair in UV-irradiated human oral keratinocytes immortalized with type 16 human papillomavirus genome.
Oncogene
; 18(50): 6997-7001, 1999 Nov 25.
Article
em En
| MEDLINE
| ID: mdl-10597299
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.
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Base de dados:
MEDLINE
Assunto principal:
Papillomaviridae
/
Queratinócitos
/
Reparo do DNA
Limite:
Humans
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article