Oxidative stress in pterygium: relationship between p53 and8-hydroxydeoxyguanosine

[摘要] Purpose: Ultraviolet (UV) radiation is known to cause oxidative DNAdamage and is thought to be a major factor implicated in thepathogenesis of pterygium, a benign invasive lesion of the bulbarconjunctiva. Among all the photooxidative DNA products,8-hydroxydeoxyguanosine (8-OHdG) is regarded as a sensitive and stablebiomarker for evaluating the degree of DNA damage. The protein p53 is amajor cell stress regulator that acts to integrate signals from a widerange of cellular stresses. UV radiation can cause mutations in the p53tumor suppressor gene that, when inactivated through mutation and lossof heterozygosity, can lead to cell proliferation and genomicinstability. In many types of UV-radiation damaged cells, p53 isoverexpressed and immunohistochemically detectable. Recent data ontissues exposed to factors inducing oxidative stress have providedevidence of the concomitant presence of increased levels of 8-OHdG andprotein p53. To verify a possible significant association between p53and 8-OHdG, we examined a series of 31 Ecuadorian pterygia for theexpression of the two markers. Moreover, we evaluated if clinicalvariables such as patient's age, gender, geographic location, anddisease stage, might play a role affecting the 8-OHdG and p53immunohistochemical staining results.Methods: Primary pterygium samples were treated forimmunohistochemical evaluations of 8-OHdG and p53 protein. Mousemonoclonal antibodies to 8-OHdG and p53 were used. Statistical analyseswere performed using the SPSS 12 statistical software package.Results: In our study, 21 (67.74%) pterygial samples were positivefor 8-OHdG staining, 11 (35.48%) specimens were positive for p53expression, and all negative control samples showed no staining. Thestaining for 8-OHdG was limited to the nuclei of the epithelial layer.No substantial staining was visible in the subepithelial fibrovascularlayers. No differences in the pattern of staining between 8-OHdG and p53were observed. All samples positive for p53 (11/31, 35.48%) were alsopositive for 8-OHdG immunostaining, and all specimens negative for8-OHdG (10/31, 32.26%) were also negative for p53. When analyzed byFisher's exact test, 8-OHdG expression was significantly associated withp53 positivity (p=0.0049). Student's t-test demonstrated statisticallysignificant association between the expression of p53 and age (p=0.02).The correlation between the two markers and the other clinical variablesrevealed no statistically significant association.Conclusions: Although pterygium is a lesion with limited localinvasion and an inability to metastasize, the concomitant presence ofaltered p53 in 8-OHdG-immunoreactive cells could provide evidence ofapparent genetic instability, which is in contrast to its benignclinical course.

[学科分类] 生物化学/生物物理