Reference SummarySansom OJ, Cancer Res 2001 Oct 1;61(19):7060-4

Title

 Suppression of intestinal and mammary neoplasia by lifetime administration of aspirin in Apc(Min/+) and Apc(Min/+), Msh2(-/-) mice.

Authors

 Sansom OJ; Stark LA; Dunlop MG; Clarke AR

Journal

 Cancer Res

Volume

 61

Issue

 19

Year

 2001

Pages

 7060-4

Abstract

 Numerous studies have indicated that exposure to nonsteroidal anti-inflammatory drugs is associated with a lowered risk of colorectal cancer. However, analyses of the effect of aspirin upon tumorigenesis in Apc(Min/+) mice have yielded contrasting results. We show that adult dietary exposure to aspirin does not suppress intestinal tumorigenesis in Apc(Min/+) mice, but that continual exposure from the point of conception does. To test whether this regime could suppress the phenotype of murine models of hereditary nonpolyposis colorectal cancer, Msh2-deficient mice were exposed to aspirin. This did not modify the mutator phenotype of Msh2(-/-) mice, but weakly extended survival. Finally, we analyzed (Apc(Min/+), Msh2(-/-)) mice and found that lifetime aspirin exposure significantly delayed the onset of both intestinal and mammary neoplasia. Thus embryonic and perinatal exposure to aspirin suppresses neoplasia specifically associated with the loss of Apc function, opening a potential window of opportunity for nonsteroidal anti-inflammatory drug intervention.

Links

 J:72233 – MGI References
11585736 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.129P2-Msh2tm1Htr Aspirin treatment slightly increased lifespan from maximun of 305 days to 325 days.
No change in mutation frequency at Galgt2b [Dlb-1b] locus in intestines of mice fed aspirin for 4 months.
These B6.129P2-Msh2tm1Htr mice were generated by backcrossing the Msh2tm1Htr mutation onto 2 differernt substrains of C57BL/6 (one homozygous for Galgt2a [Dlb-1a] and the other homozygous for Galgt2b [Dlb-1b]) and then intercrossing the progeny to get mice heterozygous at the Galgt2 locus and segregating for all possible Msh2 genotypes.
C57BL/6 Mice are homozygous for C57BL/6 derived Pla2g2a, which may render them slightly resistant to intestinal tumorigenesis.
C57BL/6-ApcMin/+ Aspirin treatment did not appear to cause embryonic lethality in ApcMin/+ mice as previously reported.
Mice are homozygous for C57BL/6 derived Pla2g2a, which may render them slightly resistant to tumorigenesis.
Part of a cohort study. Mice were generated by crossing C57BL/6-ApcMin/+ with B6.129P2-Msh2tm1Htr mice and intercrossing the subsequent offspring. Background includes multiple substrains of C57BL/6 and 129P2/OlaHsd.
Treatment with 400mg/kg aspirin from conception extends average lifespan from 175 days to 330 days.
C57BL/6-ApcMin/+ Msh2tm1Htr Part of a cohort study. Mice were generated by crossing C57BL/6-ApcMin/+ with B6.129P2-Msh2tm1Htr mice and intercrossing the subsequent offspring. Background includes multiple substrains of C57BL/6 and 129P2/OlaHsd.
Treatment with 400mg/kg aspirin from conception extends average lifespan from 98 days to 127 days.
C57BL/6-Msh2tm1Htr Part of a cohort study. These mice were generated by crossing C57BL/6-ApcMin/+ with B6.129P2-Msh2tm1Htr mice and intercrossing the subsequent offspring. Background includes multiple substrains of C57BL/6 and 129P2/OlaHsd.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6-ApcMin/+ Intestine - Large Intestine adenoma
  • aspirin (acetylsalicylic acid) (ASA)
 Intestine - Large Intestine

observed
C57BL/6-ApcMin/+ Intestine - Small Intestine adenoma
  • aspirin (acetylsalicylic acid) (ASA)
 Intestine - Small Intestine

observed - 69
C57BL/6-ApcMin/+ Intestine - Small Intestine adenoma Intestine - Small Intestine

observed
C57BL/6 Intestine adenoma Intestine

0
C57BL/6 Intestine adenoma
  • aspirin (acetylsalicylic acid) (ASA)
 Intestine

0
C57BL/6-ApcMin/+ Msh2tm1Htr Intestine adenoma
  • aspirin (acetylsalicylic acid) (ASA)
 Intestine

100
C57BL/6-ApcMin/+ Msh2tm1Htr Intestine adenoma Intestine

100
C57BL/6-Msh2tm1Htr Intestine adenoma Intestine

100
C57BL/6-Msh2tm1Htr Intestine adenoma
  • aspirin (acetylsalicylic acid) (ASA)
 Intestine

100
C57BL/6-ApcMin/+ Intestine adenoma
  • aspirin (acetylsalicylic acid) (ASA)
 Intestine

100
C57BL/6-ApcMin/+ Intestine adenoma Intestine

100
B6.129P2-Msh2tm1Htr Intestine tumor Intestine

11
C57BL/6-ApcMin/+ Leukocyte lymphoma
  • aspirin (acetylsalicylic acid) (ASA)
 Leukocyte

observed
B6.129P2-Msh2tm1Htr Leukocyte lymphoma Leukocyte

100
B6.129P2-Msh2tm1Htr Leukocyte lymphoma
  • aspirin (acetylsalicylic acid) (ASA)
 Leukocyte

100
C57BL/6-ApcMin/+ Leukocyte lymphoma Leukocyte

observed
C57BL/6-ApcMin/+ Mammary gland acanthoma Mammary gland

6.7
C57BL/6-Msh2tm1Htr Mammary gland acanthoma Mammary gland

0
C57BL/6-ApcMin/+ Msh2tm1Htr Mammary gland acanthoma Mammary gland

27
C57BL/6-Msh2tm1Htr Mammary gland acanthoma
  • aspirin (acetylsalicylic acid) (ASA)
 Mammary gland

4.8
C57BL/6-ApcMin/+ Msh2tm1Htr Mammary gland acanthoma
  • aspirin (acetylsalicylic acid) (ASA)
 Mammary gland

25
C57BL/6-ApcMin/+ Mammary gland acanthoma
  • aspirin (acetylsalicylic acid) (ASA)
 Mammary gland

0