Experimental Studies on Local Carcinogenesis in Mammary Glands with Local Dusting of DMBA-Powder

Abstract

To the 5 th right mammary gland of Sprague-Dawley female rats aged 6 weeks,1 mg of 7,12-Dimethylbenz (a) anthracene (DMBA) was administered by means of either a dusting of powder, an implantation of pressed pellet, an injection of oily solution, or an injection of emulsion. At the site of administration either adenocarcinoma or spindle cell sarcoma developed 10 months after the dusting or the transplantation, but both of the injection could induce no any mammary cancers. The induction of mammary cancer with local dusting of DMBA was more in the adult females (time of dusting: 20 weeks of age) than the young ones (time of dusting: 6 weeks of age), and it was enhanced in the females aged 7 weeks by a hypercorticoid condition.
A minute dose of some aromatic hydrocarbons was dusted on mammary fatty pads of the females aged 8 weeks. DMBA could induce mammary tumors with high incidences, but Benzo (a) pyrene,3-Methylcholanthrene or Cholesterol phosphate failed to induce any tumors 130 days after its local dusting.
The dusted sites with DMBA on mammary fatty pads of the females aged 6 weeks were observed serially from 1 day to 21 weeks after the local dusting. Necrotic foci with inflammatory changes came out immediately, and later granulation tissues with leucocytic infiltration appeared prominently. Fibrosis occurred more than 1 week after the dusting. More than 3weeks after the treatment, many of ductulal hyperplasia developed in the fibrous granulation tissues with lymphocytic infiltration. Some of the ductulal hyperplasia transfered to be papillomatous more than 5 weeks after the treatment. Finally, early adenocarcinomas evoked from some papillomatous hyperplasias of the glandular epithelium, and they made a macroscopic nodule of cancerous tissues more than 7 weeks after the local application. Half of the induced tumors were accompanied with a cellular stromal reaction. Most of the induced tumors were diagnosed as adenocarcinoma without secretory pictures. Some other tumors evoked from the DMBA-induced granulation tissues, and histological appearances of the tumors were spindle cell sarcoma.
The morphological observations on the tumorigenesis with local dusting of DMBA was discussed, in comparison of mammary carcinogenesis with systemic administration of DMBA.
Hyperplastic alveolar nodule (HAN) -like lesions were numerous in the mammary fatty tissues of almost all rats receiving intravenous injections of DMBA, but they were never seen in the rats given a local application of DMBA. Microscopic tumors originated in the mammary ducts as early as 5 weeks after local application of the carcinogen. Thus, the formation of HANs was not essential in the mammary carcinogenesis with DMBA.
Enzyme-histochemical observations were perform ed on some induced tumors with DMBA-dusting, by means of azo-dye methods for ALP, ACP, LDH or G6PDH. Atypism of these enzymic activities were detected in the apparently malignant tumors.
Biochemical determinations for LDH and MDH in the induced tumors, which were harvested 6,10 and 14 weeks after the local dusting of DMBA, indicated that the quotient of LDH/MDH in each of the same tissues was twice in the malignant tumor tissues than those of control mammary fatty pads, mammary fibroadenoma and adenoma, owing to higher LDH. The quotient elevated slightly in the earlier induced-granuloma, in which tiny microcarcinomas might be induced.