Reference SummaryJackson PE, Carcinogenesis 1999 Mar;20(3):509-13

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 PE; Cooper DP; O'Connor PJ; Povey AC

Journal

Carcinogenesis

Volume

20

Issue

3

Year

1999

Pages

509-13

Abstract

In this study we have investigated the relationship between the dose of 1,2-dimethylhydrazine (DMH) and the yield land 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-ms 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.

Links

10190570 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
SWR Intestine - Large Intestine - Anus cyst Intestine - Large Intestine - Anus

0

SWR Intestine - Large Intestine - Anus cyst
  • 1,2-dimethylhydrazine (DMH)
Intestine - Large Intestine - Anus

3.2 - 27

SWR Intestine - Large Intestine - Colon adenocarcinoma
  • 1,2-dimethylhydrazine (DMH)
Intestine - Large Intestine - Colon

0 - 87

SWR Intestine - Large Intestine - Colon adenocarcinoma Intestine - Large Intestine - Colon

2.9

SWR Intestine - Small Intestine tumor
  • 1,2-dimethylhydrazine (DMH)
Intestine - Small Intestine

0

SWR Lung lesion Lung

34

SWR Lung lesion
  • 1,2-dimethylhydrazine (DMH)
Lung

19 - 48

SWR Lung tumor
  • 3-methylcholanthrene (MCA) (3-MC)
Lung

observed

SWR Lung tumor
  • 3-methylcholanthrene (MCA) (3-MC)
  • butylated hydroxytoluene (BHT)
Lung

observed

SWR Ovary cyst Ovary

57

SWR Ovary cyst
  • 1,2-dimethylhydrazine (DMH)
Ovary

10 - 42