The relationship between 1,2-dimethylhydrazine dose and the induction of colon tumours: tumour development in female SWR mice does not require a K-ras mutational event.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91347
Title:
The relationship between 1,2-dimethylhydrazine dose and the induction of colon tumours: tumour development in female SWR mice does not require a K-ras mutational event.
Authors:
Jackson, Peta E; Cooper, Donald P; O'Connor, Peter J; Povey, Andrew C
Abstract:
In this study we have investigated the relationship between the dose of 1,2-dimethylhydrazine (DMH) and the yield (and location) of tumours in a mouse strain susceptible to colon tumour induction. Female SWR mice were injected with 6.8 mg/kg DMH i.p. once a week for 1, 5, 10 and 20 weeks and the animals were followed for almost 2 years. Administration of increasing doses of DMH resulted in a dose-dependent decrease in survival time. Colon tumours developed in 26, 76 and 87% of mice given a total dose of 34, 68 and 136 mg/kg DMH, respectively: no tumours were detected in animals treated with a total dose of 6.8 mg/kg. Most colon tumours (79%) were located in the distal colon with the remainder being found in the mid colon and none were detected in either the proximal colon or small intestine. As mutations in the K-ras gene are thought to be key events in the pathogenesis of human and rodent colon tumours, we determined the frequency of codon 12 and 13 K-ras mutations in these tumours by restriction site mutation analysis and/or DNA sequencing. A total of 50 colon tumour samples were analysed for codon 12 mutations and of these 29 were also screened for codon 13 mutations. No mutations were detected in either of these codons. The mutational activation of the K-ras gene is not an essential step in the development of DMH-induced colon tumours in female SWR mice and if similar considerations apply to humans, then the aetiological role of alkylating agents may be underestimated from the prevalence of K-ras GC-->AT transitions in human tumours.
Affiliation:
CRC Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, UK.
Citation:
The relationship between 1,2-dimethylhydrazine dose and the induction of colon tumours: tumour development in female SWR mice does not require a K-ras mutational event. 1999, 20 (3):509-13 Carcinogenesis
Journal:
Carcinogenesis
Issue Date:
Mar-1999
URI:
http://hdl.handle.net/10541/91347
DOI:
10.1093/carcin/20.3.509
PubMed ID:
10190570
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.authorCooper, Donald Pen
dc.contributor.authorO'Connor, Peter Jen
dc.contributor.authorPovey, Andrew Cen
dc.date.accessioned2010-02-08T11:17:35Z-
dc.date.available2010-02-08T11:17:35Z-
dc.date.issued1999-03-
dc.identifier.citationThe relationship between 1,2-dimethylhydrazine dose and the induction of colon tumours: tumour development in female SWR mice does not require a K-ras mutational event. 1999, 20 (3):509-13 Carcinogenesisen
dc.identifier.issn0143-3334-
dc.identifier.pmid10190570-
dc.identifier.doi10.1093/carcin/20.3.509-
dc.identifier.urihttp://hdl.handle.net/10541/91347-
dc.description.abstractIn this study we have investigated the relationship between the dose of 1,2-dimethylhydrazine (DMH) and the yield (and location) of tumours in a mouse strain susceptible to colon tumour induction. Female SWR mice were injected with 6.8 mg/kg DMH i.p. once a week for 1, 5, 10 and 20 weeks and the animals were followed for almost 2 years. Administration of increasing doses of DMH resulted in a dose-dependent decrease in survival time. Colon tumours developed in 26, 76 and 87% of mice given a total dose of 34, 68 and 136 mg/kg DMH, respectively: no tumours were detected in animals treated with a total dose of 6.8 mg/kg. Most colon tumours (79%) were located in the distal colon with the remainder being found in the mid colon and none were detected in either the proximal colon or small intestine. As mutations in the K-ras gene are thought to be key events in the pathogenesis of human and rodent colon tumours, we determined the frequency of codon 12 and 13 K-ras mutations in these tumours by restriction site mutation analysis and/or DNA sequencing. A total of 50 colon tumour samples were analysed for codon 12 mutations and of these 29 were also screened for codon 13 mutations. No mutations were detected in either of these codons. The mutational activation of the K-ras gene is not an essential step in the development of DMH-induced colon tumours in female SWR mice and if similar considerations apply to humans, then the aetiological role of alkylating agents may be underestimated from the prevalence of K-ras GC-->AT transitions in human tumours.en
dc.language.isoenen
dc.subjectColonic Canceren
dc.subject.mesh1,2-Dimethylhydrazine-
dc.subject.meshAdenocarcinoma-
dc.subject.meshAnimals-
dc.subject.meshBase Sequence-
dc.subject.meshCarcinogens-
dc.subject.meshColonic Neoplasms-
dc.subject.meshDNA Primers-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshFemale-
dc.subject.meshGenes, ras-
dc.subject.meshMice-
dc.subject.meshMutation-
dc.titleThe relationship between 1,2-dimethylhydrazine dose and the induction of colon tumours: tumour development in female SWR mice does not require a K-ras mutational event.en
dc.typeArticleen
dc.contributor.departmentCRC Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalCarcinogenesisen
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