Heterogeneity of O(6)-alkylguanine-DNA alkyltransferase activity in colorectal cancer: implications for treatment.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82467
Title:
Heterogeneity of O(6)-alkylguanine-DNA alkyltransferase activity in colorectal cancer: implications for treatment.
Authors:
Lees, Nicholas P; Harrison, Kathryn L; Hill, Elizabeth; Hall, C Nicholas; Povey, Andrew C; Margison, Geoffrey P
Abstract:
OBJECTIVES: MGMT (O(6)-alkylguanine-DNA alkyltransferase) reverses the carcinogenic, mutagenic and cytotoxic effects of alkylating agents. Measurement of MGMT activity in tumours might thus be of use in selecting those patients with colorectal cancer who may be sensitive to adjuvant alkylating agent therapy. The aim of this study was to assess whether measurement of MGMT activity in a single tumour biopsy is representative of the whole tumour. METHODS: Multiple symmetrically spaced biopsies were taken from colorectal cancers obtained from 9 patients. MGMT activity was then measured in cell-free extracts by quantifying the transfer of [(3)H]methyl group from calf thymus DNA methylated in vitro with N-nitroso-N-[(3)H]-methylurea to the MGMT protein. RESULTS: MGMT activity was detected in all tumour samples with the activity ranging between 3.6 and 36.2 fmol/microg DNA and 202-1,986 fmol/mg protein. Heterogeneity in MGMT activity (ratio of maximum/minimum MGMT levels per tumour) varied between 1.3 and 5.4. CONCLUSIONS: Measurement of MGMT activity in a single biopsy is not necessarily indicative of the level throughout the tumour. The response of colorectal cancers to alkylating agent treatment is likely to be non-uniform both within the tumour and between patients.
Affiliation:
Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, The University of Manchester, UK.
Citation:
Heterogeneity of O(6)-alkylguanine-DNA alkyltransferase activity in colorectal cancer: implications for treatment. 2002, 63 (4):393-7 Oncology
Journal:
Oncology
Issue Date:
2002
URI:
http://hdl.handle.net/10541/82467
DOI:
10.1159/000066221
PubMed ID:
12417795
Type:
Article
Language:
en
ISSN:
0030-2414
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLees, Nicholas P-
dc.contributor.authorHarrison, Kathryn L-
dc.contributor.authorHill, Elizabeth-
dc.contributor.authorHall, C Nicholas-
dc.contributor.authorPovey, Andrew C-
dc.contributor.authorMargison, Geoffrey P-
dc.date.accessioned2009-09-24T10:22:15Z-
dc.date.available2009-09-24T10:22:15Z-
dc.date.issued2002-
dc.identifier.citationHeterogeneity of O(6)-alkylguanine-DNA alkyltransferase activity in colorectal cancer: implications for treatment. 2002, 63 (4):393-7 Oncologyen
dc.identifier.issn0030-2414-
dc.identifier.pmid12417795-
dc.identifier.doi10.1159/000066221-
dc.identifier.urihttp://hdl.handle.net/10541/82467-
dc.description.abstractOBJECTIVES: MGMT (O(6)-alkylguanine-DNA alkyltransferase) reverses the carcinogenic, mutagenic and cytotoxic effects of alkylating agents. Measurement of MGMT activity in tumours might thus be of use in selecting those patients with colorectal cancer who may be sensitive to adjuvant alkylating agent therapy. The aim of this study was to assess whether measurement of MGMT activity in a single tumour biopsy is representative of the whole tumour. METHODS: Multiple symmetrically spaced biopsies were taken from colorectal cancers obtained from 9 patients. MGMT activity was then measured in cell-free extracts by quantifying the transfer of [(3)H]methyl group from calf thymus DNA methylated in vitro with N-nitroso-N-[(3)H]-methylurea to the MGMT protein. RESULTS: MGMT activity was detected in all tumour samples with the activity ranging between 3.6 and 36.2 fmol/microg DNA and 202-1,986 fmol/mg protein. Heterogeneity in MGMT activity (ratio of maximum/minimum MGMT levels per tumour) varied between 1.3 and 5.4. CONCLUSIONS: Measurement of MGMT activity in a single biopsy is not necessarily indicative of the level throughout the tumour. The response of colorectal cancers to alkylating agent treatment is likely to be non-uniform both within the tumour and between patients.en
dc.language.isoenen
dc.subjectColorectal Canceren
dc.subject.meshAdenocarcinoma-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.titleHeterogeneity of O(6)-alkylguanine-DNA alkyltransferase activity in colorectal cancer: implications for treatment.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, The University of Manchester, UK.en
dc.identifier.journalOncologyen

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