SOME BIOLOGICAL PROBLEMS IN CANCER BIOCHEMISTRY

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Abstract
Understanding of the cancer process in chemical terms has been seriously hampered by the difficulty of interpreting results of biochemical comparisons between masses of tumor and of normal tissue. Normal tissue consists of a variety of cell types and tumors may originate from one or more of these. As whole masses, therefore, normal tissues cannot serve as adequate controls for experiments on any single tumor. Tumor cell populations, even those arising from a single cell type, are themselves cytogenetically and continually undergoing changes during growth (progression). It is thus difficult, if not impossible, to separate the relevant from the irrelevant biochemical features of malignancy.Progress in this field requires means of dealing with the problem of biological heterogeneity. Several biochemical approaches that are free from the hazards of heterogeneity and which have already yielded valuable results, or appear promising, are indicated. These include: (1) The use of ascites tumors for studying the biochemical machinery of cells. No normal tissue exists, however, that could serve as satisfactory control. (2) Biochemical comparisons between pairs of tumor lines which differ by only one inherited characteristic of malignancy. These might reveal a biochemical basis for the biological properties of tumor cells with different degrees of malignancy. (3) Elucidation of normal growth-controlling mechanisms between cells, e.g. action of hormones at the cellular level, and within cells, e.g. mechanism of feed-back control of enzymes and metabolic pathways. (4) Further research into the biochemistry of plant tumor induction in vitro. Here biochemical changes associated with inherited changes leading to nutritional autonomy and uncontrolled growth have already been demonstrated. (5) Studies on the biochemical events during induction of malignancy by viruses in clonal cultures of animal cells in vitro. These could serve as useful models of the whole process of carcinogenesis.