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A Series of Transplantable Rat Mammary Tumors with Graded Differentiation, Growth Rate, and Glutaminase Content¹

The Cancer Research Institute, New England Deaconess Hospital, the Department of Biological Chemistry, Harvard Medical School, and the Department of Pathology, Boston University School of Medicine, Boston, Massachusetts 02215

A series of nine transplantable rat mammary tumors of spontaneous origin or induced by chemicals or radiation were ranked by their degree of morphological undifferentiation, exponential rate of growth in volume, and content of phosphate-dependent glutaminase (kidney-type) activity. Glutaminase was absent from normal virgin or lactating mammary glands but present in all the tumors. The specific activity of glutaminase, a mitochondrial enzyme, was high because mitochondrial protein was low in the tumors. Carried in either male or female rats, the tumors ranged from well-differentiated to undifferentiated carcinomata and covered a 10-fold range in growth rates and a six-fold range in glutaminase content per cell. Growth rates were proportional to the glutaminase content per cell or per gram, and these two properties were significantly correlated (r = 0.904; p < 0.001). Both properties were also proportional and significantly correlated to the degrees of histological undifferentiation of the tumors (r = 0.768 and 0.672 respectively). The series presents a spectrum of reproducible neoplastic behavior from a single organ, characterized quantitatively by the correlated morphology, growth, and enzyme content of the individual tumors.

¹ This investigation was supported by USPHS, Grant CA-06993, NIH General Research Support Grant of the National Cancer Institute, NIH Research Career Award AM-K6-2018 from the National Institute of Arthritis and Metabolic Diseases, and U. S. Atomic Energy Commission Contracts AT(30-1)-3779 and AT(30-1)-3777 with the New England Deaconess Hospital.

² Formerly Maria Linder-Horowitz. Present address: Department of Nutrition, Massachusetts Institute of Technology, Cambridge, Mass. 02139.

Received 2/27/69. Accepted 7/16/69.