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Biochemical Characteristics of Mammary Glands and Mammary Tumors of Rats Induced by 3-Methylcholanthrene and 7,12-Dimethylbenz(a)anthracene¹

Squibb Institute for Medical Research (R. H., H. G., I. M., M. J. C., C. B.), New Brunswick, New Jersey 08903, and Fels Research Institute (M. G., D. R. M., M. B. S.), Temple University School of Medicine, Philadelphia, Pennsylvania 19140

Nucleic acids, lipids, and several enzyme activities were measured in mammary carcinomas induced in rats by 3-methylcholanthrene (MCA) or 7,12-dimethylbenz(a)anthracene (DMBA). These biochemical parameters in the neoplasms were also studied after ovariectomy of, or the administration of either estrogen or androgen to, the tumor-bearing animals. In untreated tumor-bearing animals, the levels of triglycerides and the activities of glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase were similar in MCA- and DMBA-induced tumors arising after multiple feeding of the carcinogen, but these parameters were significantly different in tumors arising after a single intubation of DMBA. Ovariectomy produced decreases of similar magnitude in several enzyme activities in both types of carcinogen-induced carcinomas, and treatment with androgen or estrogen caused changes in the biochemistry of these tumors that only in part resembled the effects observed after ovariectomy. Treatment with estrogen produced a secretory response in the DMBA-induced carcinomas, and this response was accompanied by marked elevations in malate dehydrogenase and -glycerolphosphate dehydrogenase activities, along with a 9-fold increase in triglyceride levels. No such secretory response was observed in MCA-induced neoplasms. The activities of several enzymes in the mammary glands from animals bearing DMBA-induced neoplasms were significantly reduced compared to mammary glands from control animals devoid of tumors or mammary glands of animals bearing MCA-induced neoplasms. Thus, subtle biochemical differences were found in mammary carcinomas induced by single or multiple doses of DMBA, and these biochemical differences may be related to differences in growth rate and responsiveness.

¹ Supported by Contract No. PH43-65-1050, Endocrine Evaluation Branch, General Laboratories and Clinics, National Cancer Institute, NIH, Bethesda, Maryland 20014, and in part by Grant CA-07771, National Cancer Institute, NIH, USPHS.

Received 9/17/68. Accepted 12/12/68.