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.
Affiliation
CRC Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, UK.Issue Date
1999-03
Metadata
Show full item recordAbstract
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.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 CarcinogenesisJournal
CarcinogenesisDOI
10.1093/carcin/20.3.509PubMed ID
10190570Type
ArticleLanguage
enISSN
0143-3334ae974a485f413a2113503eed53cd6c53
10.1093/carcin/20.3.509
Scopus Count
Collections
Related articles
- The potent colon carcinogen, 1,2-dimethylhydrazine induces mutations primarily in the colon.
- Authors: Newell LE, Heddle JA
- Issue date: 2004 Nov 14
- Mutational analysis of Ctnnb1 and Apc in tumors from rats given 1,2-dimethylhydrazine or 2-amino-3-methylimidazo[4,5-f]quinoline: mutational 'hotspots' and the relative expression of beta-catenin and c-jun.
- Authors: Blum CA, Tanaka T, Zhong X, Li Q, Dashwood WM, Pereira C, Xu M, Dashwood RH
- Issue date: 2003 Apr
- Mutations in the K-ras oncogene induced by 1,2-dimethylhydrazine in preneoplastic and neoplastic rat colonic mucosa.
- Authors: Jacoby RF, Llor X, Teng BB, Davidson NO, Brasitus TA
- Issue date: 1991 Feb
- 1,2-Dimethylhydrazine-induced colon carcinoma and lymphoma in msh2(-/-) mice.
- Authors: Colussi C, Fiumicino S, Giuliani A, Rosini S, Musiani P, Macrí C, Potten CS, Crescenzi M, Bignami M
- Issue date: 2001 Oct 17
- Mutant K-ras promotes carcinogen-induced murine colorectal tumourigenesis, but does not alter tumour chromosome stability.
- Authors: Luo F, Poulogiannis G, Ye H, Hamoudi R, Zhang W, Dong G, Arends MJ
- Issue date: 2011 Feb