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Autoimmunity and tumor resistance. 3-Methylcholanthrene tumorigenesis in New Zealand Black mice
Abstract:
Skin tumors induced by the subcutaneous injection of 3-methylcholanthrene (3-MC) in New Zealand Black (NZB) mice had a delayed development and lower frequency compared with BALB/c and C57BL mice. In the SJL/J strain, the incidence of tumors was lower than in the NZB, but with the same delayed development. Most of the tumors in the BALB/c, C57BL, and SJL/J strains were sarcomas; more than one third of the tumors in the NZB mice were squamous cell carcinomas. The greatest frequency and most rapid development of tumors in the NZB, as a function of age at the time of injection of 3-MC, occurred at 4 months. Young (3.5 and 7 weeks) and 12-month-old tumor incidence in the 4-month-old NZB was decreased by treatment with antithymocyte serum (ATS). Five hundred rad whole-body x-irradiation accelerated the onset of tumors but did not increase the final incidence. 3-MC injection and the presence of skin tumors had no influence on the development of glomerulonephritis or hematopoietic neoplasms in the NZB mice. Coombs' positive anemia was not influenced by 3-MC injection, but there was an earlier and increased incidence of positive Coombs' tests in tumor-bearing animals. Liver aryl hydrocarbon hydroxylase (AHH) specific activity was low in the young NZB, increased gradually with age, and was higher in the female mice.
Insights
The study investigated how 3-methylcholanthrene (3-MC) induces skin tumors in different mouse strains. Tumor development varied by strain, with NZB mice showing delayed onset and different tumor types, but incidence decreased with antithymocyte serum treatment.
Area of Science:
- Immunology
- Toxicology
- Oncology
Background:
- 3-methylcholanthrene (3-MC) is a potent carcinogen used to induce skin tumors in experimental models.
- Different mouse strains exhibit varying susceptibilities to chemically induced cancers.
- Understanding strain-specific responses to carcinogens is crucial for cancer research.
Purpose of the Study:
- To compare the incidence, development, and type of 3-MC-induced skin tumors across different mouse strains (NZB, BALB/c, C57BL, SJL/J).
- To investigate the influence of age at carcinogen exposure on tumor development in NZB mice.
- To evaluate the effects of antithymocyte serum (ATS) and whole-body x-irradiation on 3-MC-induced tumorigenesis in NZB mice.
Main Methods:
- Subcutaneous injection of 3-methylcholanthrene (3-MC) into various mouse strains.
- Assessment of tumor incidence, latency, and histological type.
- Evaluation of tumor development in NZB mice at different ages and following ATS treatment or x-irradiation.
- Monitoring for non-neoplastic conditions like glomerulonephritis, hematopoietic neoplasms, and Coombs' positive anemia.
Main Results:
- NZB mice exhibited delayed and less frequent skin tumor development compared to BALB/c and C57BL mice, with a higher proportion of squamous cell carcinomas.
- Tumorigenesis in NZB mice was most frequent and rapid when 3-MC was administered at 4 months of age.
- Antithymocyte serum (ATS) treatment decreased tumor incidence in 4-month-old NZB mice, while x-irradiation accelerated tumor onset without altering final incidence.
- 3-MC injection and skin tumors did not affect glomerulonephritis or hematopoietic neoplasms but were associated with earlier and increased incidence of Coombs' positive anemia.
Conclusions:
- Mouse strain genetics significantly influence the development and type of 3-MC-induced skin tumors.
- Age at exposure and immunomodulation (ATS) impact carcinogen-induced tumorigenesis in NZB mice.
- While 3-MC did not affect certain autoimmune conditions, it correlated with altered immune responses indicated by Coombs' tests.