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Lactate Dehydrogenase Subunits in Normal and Neoplastic Tissues of the Rat¹

Fels Research Institute, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, and the National Cancer Institute, Bethesda, Maryland 20014

A kinetic procedure, based on differences in affinity of lactate dehydrogenase (LDH) subunits for L(+)-lactate, was employed to measure the M and H subunit activities of this enzyme in a variety of normal and neoplastic tissues of the rat. Total LDH activity was highest in liver (both normal and regenerating) at about 150 units per gm fresh tissue and somewhat lower in heart and femoral muscle at about 100 units per gm. All other tissues had less than 50 units per gm and decreased in the order: uterus during pregnancy, spleen, kidney, lactating mammary gland, brain, diaphragm, uterus, thymus, lung, testes, and mammary gland during pregnancy. The proportion of the M form was highest in both normal and regenerating liver at >90% and was also predominant in femoral muscle, spleen, uterus, diaphragm, thymus, and lung. The lactating mammary gland had about 10 times as much M form but the same H form activity as the gland of pregnancy; the uterus of pregnancy had about 3 times the M form but about the same H form activity as the normal uterus. The H form was predominant in heart, kidney, brain, and testes but made up no more than about 60% of the total. Highly differentiated, slow-growing, transplantable hepatomas had relatively low total LDH activities, at about 50 units per gm, whereas poorly differentiated, rapid-growing tumors had activities between 125 and 160 units per gm. Well-differentiated tumors of intermediate growth rates had intermediate total LDH levels. Although all hepatic tumors displayed predominant M form activity, ranging from 69 to 100%, there was no consistent pattern in relation to growth rate or degree of differentiation. Three transplantable kidney tumors had two to four times as much M form activity but about the same H form activity as normal kidney; 2,6-dimethyl-benzanthracene- and 3-methylcholanthrene-induced primary mammary tumors had similar M and H form activities as lactating mammary gland. These data are in accord with previous conclusions, based on electrophoretically determined isozyme distributions, that tumors in general have a preponderance of the M form; however, there was no clear correlation between either the total or subunit proportion of LDH activity on the one hand and growth rate or degree of differentiation on the other.

¹ Aided by grants CA-07174, CA-10439, CA-10729, and AM-05487 from the NIH and P-202 from the American Cancer Society.

² This work was carried out while one of us, Adolfo Rosado, was on leave from the Instituto Mexicano del Seguro Social. It will be included in a thesis to be submitted to the Graduate Council of Temple University in partial fulfillment of the requirements for the Ph.D. degree.

³ Present address: Department of Biochemistry, Howard University School of Medicine, Washington, C. C. 20001.

Received 1/ 7/69. Accepted 5/ 9/69.