39 research outputs found
Antioxidant enzyme levels in cancer
Normal cells are protected by antioxidant
enzymes from the toxic effects of high concentrations of
reactive oxygen species generated during cellular
metabolism. Even though cancer cells generate reactive
oxygen species, it has been demonstrated biochemically
that antioxidant enzyme levels are low in most animal
and human cancers. However, a few cancer types have
been found to have elevated levels of antioxidant
enzymes, particularly manganese superoxide dismutase.
Morphologic studies of animal and human cancer have
confirmed that although the majority of tumor cell types
from severa1 organ systems have low antioxidant
enzymes, adenocarcinomas may have elevated
manganese superoxide dismutase and catalase levels.
However, al1 cancers examined to date have some
imbalance in antioxidant enzyme levels compared with
the cell of origin. Antioxidant enzyme importance in
cancer genesis has been difficult to evaluate in early
cancerous lesions using biochemical techniques because
such lesions are small and therefore below the leve1 of
detection. Using immunohistochemical techniques, early
lesions of human and animal cancers were demonstrated
to have low antioxidant enzymes, thus suggesting a role
for these enzymes both in the genesis of cancer and the
malignant phenotype. Al1 but one human cancer cell
type (the granular cell variant of human renal
adenocarcinoma) examined showed both low catalase
and glutathione peroxidase levels, suggesting that
most cancer cell types cannot detoxify hydrogen
peroxide. Our results to date are used to propose new
cancer therapies based on modulation of cellular redox
state
lmmunogold analysis of antioxidant enzymes in common renal cancers
Immunogold studies of normal human
kidney and common human kidney cancers were
performed using polyclonal antibodies to antioxidant
enzymes, including antibodies to copper, zinc and
manganese superoxide dismutases, catalase, glutathione
peroxidase, and glutathione S-transferases and their
subunits. Normal tissue adjacent to human renal tumors
had the same antioxidant enzyme immunoreactive
protein profiles as normal human kidney, thus
establishing that the presence of tumor does not alter the
levels of antioxidant enzyme immunoreactive proteins in
adjacent kidney tissue. Levels of immunoreactive
protein for antioxidant enzymes were determined in four
common types of malignant renal cancer. In general,
tumors had low levels of antioxidant enzymes; however,
certain histologic types of renal tumors had high levels
of immunoreactive protein for glutathione S-transferase
subunits, which could affect their susceptibility to
chemotherapy. Studies of transitional carcinoma of the
renal pelvis were especially informative since it was
possible to compare levels of antioxidant enzyme
immunoreactive protein with adjacent normal
transitional epithelium; the majority of antibodies
resulted in lower levels of immunoreactive protein in
transitional cell carcinoma than in adjacent normal
transitional epithelium. Our results are discussed in
relation to the response of renal tumors to therapy
An immunohistochemical analysis of antioxidant and glutathione S-transferase enzyme levels in normal and neoplastic human lung
Samples of normal human lung and six major
types of human lung carcinomas were immunostained
for antioxidant enzymes (manganese and copper, zinc
superoxide dismutases, catalase, and glutathione
peroxidase) and six isoenzymes of glutathione Stransferase
staining was generally low in tumor cells
compared with the high level of staining noted in
respiratory epithelium. A notable exception was
heterogeneity in immunostaining for manganese
superoxide dismutase in lung adenocarcinoma, which
showed both positive and negative cells in the same
tumor. Tumor stromal cells (fibroblast-appearing cells)
often showed strong immunostaining for manganese
superoxide dismutase, while stromal cells were negative
for other antioxidant and glutathione S-transferase
enzymes. None of the carcinomas studied had significant
levels of catalase or glutathione peroxidase; this finding
has potential clinical relevance since it indicates that
these tumors cannot detoxify hydrogen peroxide. The
low levels of antioxidant and glutathione S-transferase
enzymes in tumor cells is consistent with the hypothesis
that these enzymes are markers of cell differentiation
Transfection and Expression of MnSOD cDNA Decreases Tumor Malignancy of Human Oral Squamous Carcinoma SCC-25 Cells
Inhibition of tumor cell growth by overexpression of manganese-containing superoxide dismutase
Mössbauer effect studies following Coulomb excitation using a closed cycle helium refrigerator
Immunolocalization and Adenoviral Vector-mediated Manganese Superoxide Dismutase Gene Transfer to Experimental Oral Tumors
The anti-oxidant enzyme system protects cellular macromolecules against damage from reactive oxygen species. One component of this system, manganese superoxide dismutase (MnSOD), has also been shown to display tumor suppressor gene-like activity. The purpose of this study was to examine changes in MnSOD expression during hamster cheek pouch carcinogenesis, and the effects of MnSOD overexpression using an adenoviral vector. Tumor induction was carried out using 7,12-dimethylbenz[α]anthracene. Animals were killed at periodic intervals, and check pouch tissues were excised and examined for MnSOD expression by immunohistochemistry and digital image analysis. We observed a reduction in MnSOD expression as early as 2 weeks after the start of carcinogen application. Low MnSOD expression persisted until the end of the 23-week experimental period. Solid hamster cheek pouch carcinoma xenografts were then established in nude mice. An adenoviral vector encoding the human MnSOD gene was delivered to the xenografts by direct injection. We observed high, immediate expression of MnSOD in the xenografts that persisted for 10 days following cessation of viral construct delivery. Delivery of the MnSOD construct resulted in a maximal 50% reduction in tumor growth compared with untreated controls. Our results suggest that MnSOD may be a tumor suppressor gene in the hamster cheek pouch model system. </jats:p