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The development of contact hypersensitivity in mouse skin is suppressed by tumor promoters
B Czerniecki1, G Witz, C Reilly
1UMDNJ-Robert Wood Johnson Medical School/Rutgers University, Department of Environmental and Community Medicine, Piscataway 08854.
Abstract:
The ability of tumor promoters to suppress the development of contact hypersensitivity (CHS) was assessed by the mouse ear swelling assay. Application of the complete or second stage tumor promoters phorbol-12-myristate-13-acetate (PMA, 2 micrograms), croton oil (1%), benzoyl peroxide (20 mg), mezerein (2 micrograms), or phorbol-12-retinoate-13-acetate (PRA, 2 micrograms) to the abdominal surface of CF-1 female mice for 1 week (three treatments) prior to the sensitization of the same location with 0.5% 1-chloro-2,4-dinitrobenzene (DNCB) resulted in a 50% suppression (p less than 0.05) of the CHS response to DNCB. The first stage tumor promoters 4-O-Me-PMA (80 micrograms), calcium ionophore A23187 (80 micrograms), hydrogen peroxide (15%) and the non-promoting analogs phorbol-12,13-diacetate (PDA, 20 micrograms), phorbol (80 micrograms) or acetone did not suppress the response. The suppression of the development of CHS caused by PMA was dependent on the promoter being applied at the site of induction and was inhibited by application of the phospholipase A2 inhibitor dibromoacetophenone (100 micrograms), the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 100 micrograms), or the antiinflammatory steroid fluocinolone acetonide (2 micrograms). Application of PMA or mezerein 24 h prior to challenge with DNCB, to the ears of mice previously sensitized with DNCB resulted in a significant enhancement of the ear swelling response by 60% and 110%, respectively, compared with controls. The results demonstrate that tumor promoters suppress the development of CHS, and suggest the possibility that second stage promotion may involve suppression of the development of a tumor specific immune response.
Insights
Second-stage tumor promoters, like phorbol-12-myristate-13-acetate (PMA), significantly suppress contact hypersensitivity (CHS) development in mice. This suppression is site-specific and involves inflammatory pathways, suggesting a role in immune response modulation.
Area of Science:
- Immunology
- Dermatology
- Toxicology
Background:
- Contact hypersensitivity (CHS) is a T-cell mediated immune response.
- Tumor promoters are agents that can enhance tumor development.
- Understanding the interaction between tumor promoters and immune responses is crucial for cancer research.
Purpose of the Study:
- To investigate the effect of tumor promoters on the development of contact hypersensitivity (CHS).
- To determine if specific stages of tumor promotion influence CHS.
- To explore the mechanisms underlying the interaction between tumor promoters and immune suppression.
Main Methods:
- The mouse ear swelling assay was used to assess CHS.
- Various tumor promoters (e.g., PMA, croton oil) and non-promoters were applied to mice.
- Inhibitors of phospholipase A2, lipoxygenase, and anti-inflammatory steroids were used to probe mechanisms.
Main Results:
- Second-stage tumor promoters (PMA, croton oil, etc.) suppressed CHS development by 50%.
- First-stage promoters and non-promoting analogs did not suppress CHS.
- PMA-induced suppression was site-dependent and inhibited by specific blocking agents.
- PMA and mezerein enhanced ear swelling when applied before challenge, suggesting a complex role.
Conclusions:
- Tumor promoters, particularly second-stage ones, can suppress the development of CHS.
- The suppression mechanism involves inflammatory pathways and is site-specific.
- These findings suggest that tumor promotion might involve suppressing anti-tumor immune responses.