Immunolocalization and adenoviral vector-mediated manganese superoxide dismutase gene transfer to experimental oral tumors

The anti-oxidant enzyme system protects cellular macromolecules against dam age from reactive oxygen species. One component of this system, manganese s uperoxide dismutase (MnSOD), has also been shown to display tumor suppresso r gene-like activity. The purpose of this study was to examine changes in M nSOD expression during hamster cheek pouch carcinogenesis, and the effects of MnSOD overexpression using an adenoviral vector. Tumor induction was car ried out using 7,12-dimethylbenz[alpha] anthracene. Animals were killed at periodic intervals, and cheek pouch tissues were excised and examined for M nSOD expression by immunohistochemistry and digital image analysis. We obse rved a reduction in MnSOD expression as early as 2 weeks after the start of carcinogen application. Low MnSOD expression persisted until the end of th e 23-week experimental period. Solid hamster cheek pouch carcinoma xenograf ts were then established in nude mice. An adenoviral vector encoding the hu man MnSOD gene was delivered to the xenografts by direct injection. We obse rved high, immediate expression of MnSOD in the xenografts that persisted f or 10 days following cessation of viral construct delivery. Delivery of the MnSOD construct resulted in a maximal 50% reduction in tumor growth compar ed with untreated controls. Our results suggest that MnSOD may be a tumor s uppressor gene in the hamster cheek pouch model system.