Background Mitochondrial manganese superoxide dismutase MnSOD, encoded by the SOD2 gene, represents a major cellular defense against environmental carcinogens that cause oxidative stress. Two single nucleotide polymorphisms -9 T>C; (V16A in the MnSOD mitochrondrial targeting sequence) and -102 C>T (in the SOD2 promoter sequence) modify risk towards various types of malignancies and overall survival. Since little is known about the effects these polymorphisms have on overall enzyme function in normal human tissue, the goal of this study was to evaluate their functional effects in cryopreserved human hepatocytes. Methods Cryopreserved human hepatocytes were genotyped for the MnSOD -9 T>C and -102 C>T polymorphisms by TaqMan allelic discrimination assays. MnSOD catalytic activities were determined in vitro in lysates derived from the hepatocytes. Results In random samplings of cryopreserved hepatocytes, 16% possessed the -9 T>C and 6% possessed polymorphism on at least one of the two alleles. -9 T>C (V16A) significantly (p<0.02) reduced MnSOD catalytic activity whereas -102C>T did not (p>0.05). Conclusion The -9 T>C (V16A) polymorphism in the MnSOD mitochrondrial targeting sequence significantly reduced MnSOD catalytic activity in cryopreserved hepatocytes, consistent with its reported associations with cancer risk and treatment.

Introduction The aim of this study was to compare the manganese superoxide dismutase (MnSOD) expression in matched tumor and normal tissue. Methods One hundred lung cancer specimens and matched normal lung parenchyma from the same patient were evaluated for MnSOD expression. Results The median normal MnSOD expression was 42% with a range of 10 to 70% which was significantly greater (p=0.001) than the median MnSOD expression in the tumor samples which was 18.8% and ranged from 1.1 to 50%. Conclusion MnSOD expression is significantly reduced in lung adenocarcinoma and squamous cell carcinoma compared to matched normal lung tissue.