Inter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumors: possible significance in nitrosourea therapy.
AffiliationCRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Manchester, UK.
MetadataShow full item record
AbstractThe 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 a rabbit 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 completely devoid of staining to cells with very intense staining. Semi-quantitatively, in the 23 high grade gliomas examined six had 1+ 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 approximately 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.
CitationInter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumors: possible significance in nitrosourea therapy. 1996, 17 (4):637-41 Carcinogenesis
- Expression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours.
- Authors: Lee SM, Harris M, Rennison J, McGown A, Bromley M, Elder RH, Rafferty JA, Crowther D, Margison GP
- Issue date: 1993
- Activity of fotemustine in medulloblastoma and malignant glioma xenografts in relation to O6-alkylguanine-DNA alkyltransferase and alkylpurine-DNA N-glycosylase activity.
- Authors: Vassal G, Boland I, Terrier-Lacombe MJ, Watson AJ, Margison GP, Vénuat AM, Morizet J, Parker F, Lacroix C, Lellouch-Tubiana A, Pierre-Kahn A, Poullain MG, Gouyette A
- Issue date: 1998 Feb
- DNA interstrand cross-linking and cytotoxicity induced by chloroethylnitrosoureas and cisplatin in human glioma cell lines which vary in cellular concentration of O6-alkylguanine-DNA alkyltransferase.
- Authors: Beith J, Hartley J, Darling J, Souhami R
- Issue date: 1997
- Immunohistological examination of the inter- and intracellular distribution of O6-alkylguanine DNA-alkyltransferase in human liver and melanoma.
- Authors: Lee SM, Rafferty JA, Elder RH, Fan CY, Bromley M, Harris M, Thatcher N, Potter PM, Altermatt HJ, Perinat-Frey T
- Issue date: 1992 Aug
- Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine.
- Authors: Belanich M, Pastor M, Randall T, Guerra D, Kibitel J, Alas L, Li B, Citron M, Wasserman P, White A, Eyre H, Jaeckle K, Schulman S, Rector D, Prados M, Coons S, Shapiro W, Yarosh D
- Issue date: 1996 Feb 15