Evaluation of CYP1B1, oxidative stress and phase II detoxification enzyme status in oral cancer progression model

口腔癌进展模型中 CYP1B1、氧化应激和 II 期解毒酶状态的评估

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作者:Anirudha R Bartake, Sachin Sarode, Sangeeta Palaskar, Amit Girme, Gargi Sarode, Samruddhi Kamble, Bindiya Narang, Pradnya Bhale

Background

Tobacco is one of the main etiological factors for oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD). CYP1B1 is an enzyme which plays a major role in the phase I detoxification of tobacco, the byproducts of which are subsequently detoxified by phase II enzymes Glutathione S Transferase (GST). We attempted to evaluate the L432V polymorphism and tissue expression of CYP1B1, along with the oxidant-antioxidant status in OSCC progression model. Method: ology: Tissue biopsies and blood samples were collected from the subjects; L432V polymorphism was evaluated by TaqMan RT-PCR, immunohistochemistry was performed on the tissue sample using CYP1B1 polyclonal primary antibody and Allred quick scoring system was used to evaluate the stained slides. Malonaldehyde (MDA) and GST activity were measured spectrophotometrically to assess oxidative-antioxidative status.

Conclusion

Tobacco users with CG and GG genotypes are at equal risk of developing oral epithelial dysplasia or OSCC and L432V polymorphism does not appear to increase the risk of malignant transformation in oral epithelial dysplasia. Moreover, tobacco users with GG genotype and tissue expression of CYP1B1 may be at a greater risk of oxidative damage.

Results

When the L432V polymorphism was analyzed, it was observed that in oral epithelial dysplasia (OED) and OSCC, CG was more common than GG genotype. Highest mean Allred score was observed in tobacco users (6.27), highest GST activity was seen in oral epithelial dysplasia (5.006 U/ml) and highest MDA activity was observed in OSCC (1553.94 nm/ml).

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