Low O6-alkylguanine DNA-alkyltransferase activity in normal colorectal tissue is associated with colorectal tumours containing a GC-->AT transition in the K-ras oncogene.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95185
Title:
Low O6-alkylguanine DNA-alkyltransferase activity in normal colorectal tissue is associated with colorectal tumours containing a GC-->AT transition in the K-ras oncogene.
Authors:
Jackson, Peta E; Hall, C N; O'Connor, Peter J; Cooper, Donald P; Margison, Geoffrey P; Povey, Andrew C
Abstract:
O6-alkylguanine DNA-alkyltransferase (ATase) provides protection against the toxic, mutagenic and carcinogenic effects of alkylating agents, principally by removing the promutagenic lesion O6-alkylguanine from DNA. Differences in ATase activity in human tissue may thus determine mutational susceptibility. As GC-->AT transitions, which can be induced by O6-alkylguanine in DNA, are commonly observed in the K-ras oncogene of alkylating agent induced animal tumours and in human colorectal tumours, we have examined whether differences in ATase activity may affect the risk of K-ras mutations in humans with colorectal tumours. NTase activity in normal tissue from individuals with a K-ras mutation in colorectal tissue and more specifically a GC-->AT transition (but not a transversion mutation) was significantly lower than that in individuals without a mutation (P < 0.01). Thus, individuals with low ATase activity in normal tissue (i.e. below the median) were at increased risk of having a transition (OR 10.1; 95% CI 1.9-99.0), but not a transversion mutation (OR 1.7; 95% CI 0.3-12.2). There were no significant differences in tumour ATase activity in individuals with or without a mutation. These results suggest that ATase can protect colorectal tissue against the mutagenic effects of alkylating agents and furthermore, that alkylating agent exposure plays a role in the aetiology of colorectal tumours containing a GC-->AT transition in the K-ras oncogene.
Affiliation:
Cancer Research Campaign Department of Carcinogenesis, Paterson Institute for Cancer Research, Manchester, UK.
Citation:
Low O6-alkylguanine DNA-alkyltransferase activity in normal colorectal tissue is associated with colorectal tumours containing a GC-->AT transition in the K-ras oncogene. 1997, 18 (7):1299-302 Carcinogenesis
Journal:
Carcinogenesis
Issue Date:
Jul-1997
URI:
http://hdl.handle.net/10541/95185
DOI:
10.1093/carcin/18.7.1299
PubMed ID:
9230271
Type:
Article
Language:
en
ISSN:
0143-3334
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorJackson, Peta Een
dc.contributor.authorHall, C Nen
dc.contributor.authorO'Connor, Peter Jen
dc.contributor.authorCooper, Donald Pen
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorPovey, Andrew Cen
dc.date.accessioned2010-03-29T15:12:09Z-
dc.date.available2010-03-29T15:12:09Z-
dc.date.issued1997-07-
dc.identifier.citationLow O6-alkylguanine DNA-alkyltransferase activity in normal colorectal tissue is associated with colorectal tumours containing a GC-->AT transition in the K-ras oncogene. 1997, 18 (7):1299-302 Carcinogenesisen
dc.identifier.issn0143-3334-
dc.identifier.pmid9230271-
dc.identifier.doi10.1093/carcin/18.7.1299-
dc.identifier.urihttp://hdl.handle.net/10541/95185-
dc.description.abstractO6-alkylguanine DNA-alkyltransferase (ATase) provides protection against the toxic, mutagenic and carcinogenic effects of alkylating agents, principally by removing the promutagenic lesion O6-alkylguanine from DNA. Differences in ATase activity in human tissue may thus determine mutational susceptibility. As GC-->AT transitions, which can be induced by O6-alkylguanine in DNA, are commonly observed in the K-ras oncogene of alkylating agent induced animal tumours and in human colorectal tumours, we have examined whether differences in ATase activity may affect the risk of K-ras mutations in humans with colorectal tumours. NTase activity in normal tissue from individuals with a K-ras mutation in colorectal tissue and more specifically a GC-->AT transition (but not a transversion mutation) was significantly lower than that in individuals without a mutation (P < 0.01). Thus, individuals with low ATase activity in normal tissue (i.e. below the median) were at increased risk of having a transition (OR 10.1; 95% CI 1.9-99.0), but not a transversion mutation (OR 1.7; 95% CI 0.3-12.2). There were no significant differences in tumour ATase activity in individuals with or without a mutation. These results suggest that ATase can protect colorectal tissue against the mutagenic effects of alkylating agents and furthermore, that alkylating agent exposure plays a role in the aetiology of colorectal tumours containing a GC-->AT transition in the K-ras oncogene.en
dc.language.isoenen
dc.subjectColorectal Canceren
dc.subject.meshColon-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshGenes, ras-
dc.subject.meshHumans-
dc.subject.meshMethyltransferases-
dc.subject.meshMutation-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshRectum-
dc.titleLow O6-alkylguanine DNA-alkyltransferase activity in normal colorectal tissue is associated with colorectal tumours containing a GC-->AT transition in the K-ras oncogene.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Carcinogenesis, Paterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalCarcinogenesisen
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