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© 1996 Oxford University Press

research-article

Inter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumours: possible significance in nitrosourea therapy

S.M. Lee 1 2 4, H. Reid 3, R.H. Elder 1, N. Thatcher 2 and G.P. Margison 1

1CRC Department of Carcinogenesis. Paterson Institute for Cancer Research, University of Manchester Manchester M13 9PT, UK
2CRC Department of Medical Oncology. Christie Hospital (NHS) Trust, University of Manchester Manchester M13 9PT, UK
3Department of Pathological Sciences, Medical School, University of Manchester Manchester M13 9PT, UK

4To whom correspondence should be addressed at: CRC Department of Medical Oncology, Christie Hospital (NHS) Trust, Manchester M20 4BX, UK

The inter- and intracellular distribution of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase) may be an important factor in the sensitivity or resistance of tumours to treatment with certain alkylating agents, including the methyltriazenes and nitrosoureas. In order to examine this issue 26 human brain tumour sections (23 high grade gliomas and three low grade gliomas) were examined for ATase expression by immunohistochemistry using arabbit anti-human ATase polyclonal antibody. Positive staining, seen as fine black granules mainly confined to the nucleus, was observed in all the glioma sections examined. There was marked cellular heterogeneity, ranging from cells completelydevoid of staining to cells with very intense staining. Semi-quantitatively, in the 23 high grade gliomas examined six had1+ staining, seven had 2 + staining and 10 had 3 + staining, whereas all three low grade gliomas had 1+ staining. These results are in contrast to published reports showing that ~35% of human brain tumour-derived cell lines and xenografts had very low levels of ATase activity and suggest that the complete lack of ATase is not a common occurrence in high grade glioma.


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