E6* oncoprotein expression of human papillomavirus type-16 determines different ultraviolet sensitivity related to glutathione and glutathione peroxidase antioxidant defence.
Clinical observations of non-melanoma skin cancer in immunocompromised patients, such as organ transplant recipients, suggest co-operative effects of human papillomavirus (HPV) and ultraviolet (UV) radiation. The aim of the present study is to evaluate UV sensitivity and DNA damage formation according to antioxidant status in HPV16-infected keratinocytes. We used SKv cell lines, infected with HPV16 and well characterized for their proliferative and tumorigenic capacities. We showed that SKv cell lines presented various E6* (a truncated form of E6) RNA levels. We demonstrated that the higher oncoprotein RNA expression level was associated with a higher resistance to solar-simulated radiation, more specifically to UVB radiation and to hydrogen peroxide. Moreover, this high resistance was associated with a low oxidative DNA damage formation after UV radiation and was related to high glutathione content and glutathione peroxidase activities. Therefore, the results of our study suggest that E6* levels could modulate the glutathione/glutathione peroxidase pathway providing a mechanism to protect HPV-infected keratinocytes against an environmental oxidative stress, such as UV radiation.
Mouret
Stéphane
S
Laboratoire Oligoéléments et Résistance au Stress Oxydant induit par les Xénobiotiques (ORSOX; UMR UJF-CEA, LRC7 CEA 8 M), Université Joseph Fourier, UFR de Médecine et Pharmacie, La Tronche, France.
Sauvaigo
Sylvie
S
Peinnequin
André
A
Favier
Alain
A
Beani
Jean-Claude
JC
Leccia
Marie-Thérèse
MT
D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D020552:Comet Assay; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000502:physiology*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays
D000975:Antioxidants; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D012313:RNA; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005978:Glutathione; D010100:Oxygen