Journal of Photochemistry and Photobiology B: Biology
Effects of intranasal phototherapy on nasal mucosa in patients with allergic rhinitis
Introduction
Phototherapy is widely used for the treatment of several immune-mediated skin diseases like atopic dermatitis and psoriasis [1]. In the last decade new applications have been developed and ultraviolet (UV) light has been applied with good results in the treatment of oral mucosal diseases, such as lichen planus and graft versus host disease [2], [3]. Recently, intranasal phototherapy with mixed UVA–UVB–visible light (mUV/vis) has been reported to be successful for the treatment of seasonal allergic rhinitis [4].
One of the main mechanisms of action of UV light is induction of DNA damage in the irradiated cells. This mechanism is responsible in part for the biological effects of UV light and consequently its therapeutic use. However, DNA damage is also implicated in the mutagenic and carcinogenic potential of UV light. Knowledge of the mutagenic risk of DNA photodamage has stimulated interest to determine the wavelengths dependent distribution of different DNA photodamage types [5], [6]. UV light is able to cause DNA damage by direct mechanisms (absorption of photons by the DNA) or by indirect mechanisms such as generation of reactive oxygen species [6]. UVC (100–280 nm) has been shown to induce direct DNA damage, mirrored by the preponderant production of promutagenic photoproducts, mainly cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6-4 PPs). UVB (280–320 nm) radiation is also acting mostly on DNA through direct excitation processes and results in the formation of CPDs and to a lesser extent of 6-4 PPs. It has been reported that UVC and UVB induced photodamage is more complex including also induction of strand breaks and oxidative DNA modifications [6], [7]. Until recently, the formation of single-strand breaks, alkali-labile lesions and oxidative DNA modifications has been considered to be the main mechanism of UVA (320–400 nm) damage. Recent data showed that UVA induces in bacteria, cultured cells and human skin the formation of CPDs but not 6-4 PPs [8].
Cells possess repair mechanism in response to UV induced DNA damage. The primary process that removes DNA damage is the nucleotide excision repair (NER) pathway. The removal of DNA base modifications via NER requires DNA damage recognition, lesion demarcation, dual asymmetrical incisions at the 5′ and 3′ sites flanking the lesion, excision of nucleotides from the single-stranded loop, containing the lesion, and gap-filling by DNA synthesis and ligation [9]. Alternatively, highly damaged cells undergo cell cycle arrest, activation of the caspase cascade and finally apoptotic cell death [10].
Although, skin diseases are successfully treated with phototherapy and data from the literature support that no significant increase in skin cancer risk is present in patients treated for decades with UVB light, no data are available regarding the effect of UV light on nasal mucosa.
In the present study we have evaluated the in vivo effect of intranasal phototherapy, by assessing DNA damage and repair in nasal mucosa.
Section snippets
Intranasal phototherapy of ragweed allergic patients
The examinations were performed during the 2005 ragweed season in Szeged, Hungary in eight ragweed allergic patients undergoing intranasal phototherapy. Positive skin prick tests and/or an elevated level of ragweed-specific IgE antibody confirmed the diagnosis. We excluded potential subjects from the study if they had any significant nasal structural abnormalities, or had had asthma, perennial rhinitis or upper or lower respiratory infection within 4 weeks prior to the beginning of the study,
Kinetics of DNA damage detected by Comet assay in patients undergoing intranasal phototherapy
Comet assay was performed on nasal cytology samples of eight allergic rhinitis patients before starting the treatment protocol, immediately after last irradiation and 10 days after last treatment. Four of the eight patients returned for the 2 month follow-up visit when nasal cytology samples were collected.
DNA damage was significantly higher in nasal cytology samples collected immediately after completing the 2 weeks treatment regimen than before starting therapy (p = 0.02 in conventional Comet
Discussion
Although, UV light has been previously successfully applied for the treatment of diseases of the oral and nasal mucosa, no data exist regarding DNA damage and repair of oral and/or nasal mucosal epithelial cells. Fornace et al have reported that bronchial fibroblasts and epithelial cells show similar DNA damage and repair as human skin fibroblasts, suggesting that DNA repair mechanism are equally efficient in all cell types [12]. The study conducted in allergic rhinitis patients undergoing
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