Cell death and oxidative stress in gliomas

In gliomas, apoptosis and necrosis are determined by a number of promoting and inhibiting factors including oxidative cell stress mediated by nitric o xide synthases (NOS) and reduced by superoxide dismutases. Therefore, in 46 gliomas (including astrocytomas, oligodendrogliomas, oligo-astrocytomas, a nd glioblastomas), the relationship of apoptosis and necrosis and the expre ssion of apoptosis-promoting (p53 bar, Fas, Fas-L) and inhibiting (bcl-2) f actors as well as of different isoforms of NOS (NOSb, NOSe, NOSi) and manga nese superoxide dismutase (MnSOD) were studied. Apoptosis was measured in s itu by the TUNEL method while expression profiles of apoptosis-related and oxidative stress-associated factors were determined by immunohistochemistry . As a defining criterion, necrosis was restricted to glioblastomas while a poptosis increased with tumour malignancy (P = 0.017) in all types of gliom as. Glial tumour cells displayed upregulation of bar, Fas, Fas-L, p53, and bcl-2 but with no significant correlation with malignancy. There was also a strong expression of NOS isoforms with upregulation of NOSe in all and of NOSb and NOSi in nearly 50% of the tumour specimens but only NOSb expressio n correlated significantly with tumour malignancy (P = 0.004). Likewise, Mn SOD was strongly expressed in all gliomas but was not correlated with tumou r grade. There was a wide variability of expression in each tumour type wit hout significant correlation between apoptosis and expression of apoptosis- associated or oxidative stress-related factors indicating that the network of regulating factors may be too complex for clear associations.