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Initiation and promotion at different ages and doses in 2200 mice. II. Decrease in promotion by TPA with ageing
British Journal of Cancer
|July 1, 1981
Summary
Ageing mice show a slower tumor response to DMBA and TPA treatments. This is due to reduced TPA efficacy in older mice, not altered initiation rates.
Area of Science:
- Oncology
- Carcinogenesis research
- Aging biology
Background:
- Chemical carcinogenesis involves initiation and promotion stages.
- The impact of aging on these stages is not fully understood.
- Previous studies (Paper I) established baseline treatment effects.
Purpose of the Study:
- To investigate the influence of mouse age on tumor development following chemical carcinogen exposure.
- To differentiate between changes in initiation versus promotion efficacy with age.
- To compare tumor incidence rates after specific treatment timings and doses across different age groups.
Main Methods:
- Utilizing data from a prior study (Paper I).
- Administering dimethylbenz[a]anthracene (DMBA) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) at specific intervals.
- Comparing tumor incidence in mice initiated at 8, 48, and 68 weeks of age.
Main Results:
- Initiation with DMBA at 68 weeks, followed by TPA, resulted in a significantly slower tumor incidence compared to initiation at 8 or 48 weeks (P < 0.0001).
- The reduced tumor incidence was attributed to decreased promotional efficacy of TPA in older mice.
- No significant changes were observed in the number of cells initiated by DMBA across age groups.
Conclusions:
- Mouse age significantly modulates the response to chemical carcinogenesis.
- The promotional stage of carcinogenesis is more sensitive to aging than the initiation stage.
- Aging reduces the effectiveness of tumor promoters like TPA.