Summary The oxy-radical scavenger enzyme manganese superoxide dismutase (MnSOD) may act in the capacity of a tumour-suppressor gene. To address the issue of its role in tumour transformation and progression in vivo, we evaluated the content of this enzyme in 33 brain tumours of neuroepithelial origin with different degrees of differentiation (WHO grade II-IV) by means of Western blot and immunohistology. Our results show that immunoreactive MnSOD increases in a direct relationship with tumour grade and is therefore inversely correlated with differentiation. The increase is induced at a pretranscriptional level and is apparently specific to brain tumours of neuroepithelial origin. Approximately 30% of grade IV tumours display low levels of MnSOD content, and preoperative radiotherapy and brachytherapy result in low amounts of enzyme. Based upon these observations, we suggest that MnSOD cannot be considered a classical tumour-suppressor gene.

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Increases in the expression of manganese‐dependent superoxide dismutase (MnSOD) have been detected in several classes of human and experimental tumors and appear to correlate with poorer prognosis in human neuro‐epithelial, ovarian and cervical tumors. To delineate the relevance of MnSOD expression to tumor‐cell growth and survival, a human MnSOD cDNA was over‐expressed in the HeLa cervical‐carcinoma cell line. MnSOD over‐expression had marginal effects on the growth of HeLa cells in standard medium, but markedly protected the cells from growth suppression and cell death in conditions of serum deprivation. Serum starvation did not affect expression of endogenous MnSOD in wild‐type HeLa cells, but was associated with increases in cell death and in the generation of intracellular oxygen radicals. By contrast, in HT29 colon‐carcinoma cells, which are relatively resistant to growth‐factor withdrawal, serum deprivation was associated with increases in MnSOD expression and activity. Together these observations suggest that MnSOD provides a mechanism for counteracting the intracellular oxidative processes that impair cell growth and viability in the context of growth‐factor withdrawal and, in this context, may promote tumor‐cell survival in vivo in conditions normally unfavorable to cell growth. Int. J. Cancer 82:145–150, 1999. © 1999 Wiley‐Liss, Inc.

The 4,4Ј-diketo-␤-carotene, canthaxanthin, alters tocopherol status when fed to Balb/c mice, suggesting an involvement of carotenoids in the modulation of oxidative stress in vivo. We investigated further the modifications induced by an oral administration of canthaxanthin on lipid peroxidation, antioxidant enzymes and iron status in liver of Balb/c mice. Female 6-wk-old Balb/c mice were randomly divided into two groups (n ϭ 10/group). The control group (C) received olive oil alone (vehicle) and the canthaxanthin-treated group (Cx) received canthaxanthin at a dose of 14 g/(g body wt⅐d). The 15-d canthaxanthin treatment resulted in carotenoid incorporation but did not modify lipid peroxidation as measured by endogenous production of malondialdehyde (MDA). However, glutathione peroxidase activity was 35% lower (P Ͻ 0.01) and catalase (59%, P Ͻ 0.005) and manganese superoxide dismutase (MnSOD) (28%, P Ͻ 0.05) activities were higher in canthaxanthin-treated mice than in controls. Moreover, carotenoid feeding caused a significant (P Ͻ 0.05) overexpression of the MnSOD gene; mRNA levels of the enzyme were greater in treated mice than in controls. Concomitantly, a 27% (P Ͻ 0.05) greater iron concentration was found in liver from canthaxanthin-treated mice compared with controls. These findings support the hypothesis that canthaxanthin alters the protective ability of tissues against oxidative stress in vivo.