We have previously demonstrated through immunological analysis that administration of bacterial components, gelatin, and polymerized gelatin or its derivatives can induce low-specificity anti-transplant immunity against Ehrlich carcinoma, sarcoma 180, and skin isografts in mice 1-3). Since Ehrlich carcinoma cells have been successfully transplanted in various strains of mice, they can be transplanted without the worry of being rejected by immunological mechanisms and are thus suitable for readily inducing a tumor-bearing state. These cells are recognized as allogeneic or autogeneic and are thus used as a research model for idiopathic carcinoma. However, once resistance to Ehrlich carcinoma transplants is established, the question arises whether the aforementioned immunological phenomenon is related to the fact that Ehrlich carcinoma is not a primary carcinoma, but rather a transplanted one. In other words, is the same immunological phenomenon observed in primary carcinoma cells induced by a carcinogen in the same animal? We tested this hypothesis in a rat model of mammary carcinoma induced by the carcinogen 9,10-dimethyl-1,2-benzanthracene (DMBA).

Methods and results

Gavage administration of 10 mg of DMBA dissolved in sesame oil to 6-week-old SD rats every 7 days for a total of 2 doses usually produces mammary carcinoma in 60% of rats within 2?3 months, with 80% of rats developing some type of carcinoma, such as mammary carcinoma, eustachian carcinoma, leukemia, fibroma, or adenoma. Here, no carcinoma occurred in any of the 7 rats that received 7 subcutaneous injections of 2 ml of 1% aqueous solution of acid-polymerized porcine skin gelatin every 7 days prior to DMBA (0%), whereas administration of DMBA followed by 7 subcutaneous injections under the same condition resulted in mammary carcinoma in 2 of 5 rats (40%). When 7 gelatin injections were given after DMBA administration, mammary carcinoma occurred in 1 of 4 rats (25%). In the control group, where only DMBA was administered, 3 of 6 rats (50%) developed mammary carcinoma.

Discussion

Although administration of polymerized gelatin reduced the occurrence of DMBA-induced mammary carcinoma, this observation is not adequate to draw a conclusion. Regardless of whether or not the altered immune status following the administration of polymerized gelatin affected the carcinogenic mechanism of DMBA, emerging carcinoma cells were rejected by the aforementioned anti-transplant immunity at a very early stage of tumor-bearing state. The fact that polymerized gelatin was more effective when given before, rather than after, the administration of DMBA suggests that its effect is not simply mediated by its pharmacologic activity.