The control of cell mass and replication. The DNA unit--a personal 20-year study

Abstract

The deoxyribonucleic acid (DNA) is constant per cell in diploid tissues and in polyploid tissues the DNA content and the cytoplasm increase commensurately. In muscle the DNA unit (protein/DNA) was described on the assumption that each nucleus has jurisdiction over a certain volume of cytoplasm. Such an approach allows a sensible interpretation of metabolic data. Since 66-70% of nuclei are within myofibres muscle represents a reasonably homogeneous tissue. A brief historical review is made concerning the use of DNA as a cell constant. The application of this knowledge to normal human somatic growth and to disease states is considered as well as reduced nutrition and overnutrition. The consequences of reduced nutrition as it related to brain growth are briefly mentioned as is our 7 year study on the fetal primate (Macaca mulatta). Attention is focussed on our work in the early 1960's concerning the role of insulin and growth hormone on the DNA unit. In the last decade this work culminated in the close study of the Little Mouse with isolated growth hormone deficiency--thus exposing the panhypopituitary model (the human pituitary dwarf, Snell Smith mouse or hypophysectomised rat) as non-optimal models. The findings indicate that growth hormone is indeed related to cell replication and insulin to cytoplasmic growth in the postnatal period but the role of other hormones is clearly important, augmenting or opposing these hormones. The concept of constant change of the DNA unit not only applies to major tissues such as muscle but to the study of kidney growth when the contralateral kidney is removed (renal compensatory growth). Species differences are noted in the pattern of cell growth in muscle, but emphasis is placed on cell replication rather than on cytoplasmic growth in the primate. Restriction of protein energy metabolism mainly affects cytoplasmic growth of muscle but restoration of growth to expected levels is the rule. Overnutrition and obesity relate to excessive growth of DNA units in number rather than size. Attention is drawn to factors other than calories, proteins and hormones that influence hormonal actions viz. trace metals such as zinc, chromium and vanadium. The cell mass of the body can readily be reached by relatively non-invasive methods and by monitoring the intracellular water. Muscle mass can be precisely measured by creatinine excretion. The cell mass of muscle constitutes 70% of the entire cell mass.(ABSTRACT TRUNCATED AT 400 WORDS)