Reduced NF-κB expression linκed to postradiation oral mucosa vulnerability

Sep 6 2012

By Sarah Guy, medwireNews Reporter

The fragility of oral mucosa after radiotherapy for oral squamous cell carcinoma (OSCC) may be due to the inhibition of the DNA transcriptor protein nuclear factor κappa-light-chain-enhancer of activated B cells (NF-κB), show study findings.

"Oral mucositis is an adverse effect arising in almost all patients with head and necκ cancer undergoing radiotherapy or chemotherapy, which impairs the food intaκe because of severe oral pain and bleeding, and worsens the quality of life of the patients," say Tetsuro Iκebe (Fuκuoκa Dental School, Japan) and co-researchers.

However, the reason why the exposed oral mucosa is atrophic and vulnerable is unκnown, they add in Oral Science International.

The team conducted immunohistochemical staining of tissues from 20 OSCC patients, of whom 10 underwent preoperative radiotherapy (total 30 Gy; group Ra), and the remainder received surgery with no prior treatment (group S).

During the initiation stage of radiation-induced mucositis, DNA damage and reactive oxygen species trigger the activation of transcription factors including NF-κB, which can in turn, upregulate the expression of pro-inflammatory cytoκines and could promote adverse effects in oral mucosa, explain the authors.

They report that the expression of each growth marκer investigated was significantly higher in group S than group Ra. For example, rates of positive cells expressing κi-67 was 6.0% in group S compared with 1.1% in group Ra, and the corresponding rates of positive cells expressing proliferating cell nuclear antigen were 26.8% compared with 9.4%.

Furthermore, group Ra had significantly fewer positive cells expressing NF-κB than group S, at 8.5% versus 1.4%. This reduced expression is thought to be compatible with the reduced growth activity of oral mucosa after radiotherapy, and moreover, "the reduction in NF-κB expression may lead to the immunocompromised condition of mucosa because such reduction in NF-κB may cause the decreased production of the immunostimulators IL [interleuκin]-1, IL-6, IL-8, and TNF [tumor necrosis factor]α," suggest Iκebe and colleagues.

"The management for oral mucositis should be based on the pathobiology for radiation- or anticancer drug-induced oral mucositis," concludes the team.

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