CANCER BIOLOGY: COMPARATIVE and GENETIC*

Publisher Website
Google Scholar
Abstract
SUMMARY: I employ cancer in a broad sense to cover all products of malignant neoplasia– carcinomas, sarcomas, leukaemias and ascites tumours–and tumour to cover all autonomous neoplasms. Cancer is not a biological entity, but an assemblage of many distinct diseases (malignant tumours) which share the following symptoms: (a) replication of abnormal tissue type, but often with change towards greater malignancy; (b) non‐limited proliferation; (c) some degree of histological and physiological dedifferentiation;(d) partial or often complete lack of organization; (c) invasiveness, often accompanied by metastasis. Neoplasia also includes the development of benign tumours, which exhibit symptoms (a)‐(d) above, and have therefore acquired autonomy. Neoplasia does not involve an abnormal form of tissue differentiation, but a characteristic deviation of metabolism which may affect any type of tissue. Tumours retain the specific determination of the tissues from which they arise, though in hypoplastic manifestation. Tumorigenic metabolic deviation proceeds by a series of individual chance (mutational) events, instead of by a continuous (statistical) process affecting all cells simultaneously as in normal differentiation. All autonomous neoplasms can be regarded as the equivalents of new biological species. Though the tumours of lower vertebrates, invertebrates and plants often differ in various ways from those of mammals and birds, there is no reason for regarding them as irrelevant to the human cancer problem. They are autonomous and often malignant neoplasms, and have sometimes been experimentally induced. Neoplastic tumours, whether spontaneous (in nature) (S), experimentally induced (E), or genetically induced (G), have been recorded in the following groups of organisms: The ‘cancer spectrum’ may differ markedly in different groups, species and breeds. High cancer‐proneness exists in some animal species (e.g. dogs, mice, budgerigars, domestic fowls, poecilid and cyprinodont fish) and breeds (retrievers, grey horses, some domesticated goldfish), and low cancer‐proneness in others (guinea‐pigs, rabbits, pigs, primates; Pekinese, chows). Thyroid tumours develop frequently in salmonids and some other fish in water of low oxygen content. Their invasiveness is usually not an effect of malignancy, but of the absence of a capsule in the fish thyroid. Attention is drawn to the favourable material for cancer research provided by regions of high localized growth rate (horns, horn cores, antlers, etc.), growth gradients (crustacean appendages and abdomina, molluscan mantle edges, etc.), endocrine‐dependent growth and regression (fowl‐combs, larval and metamorphosing Amphibia, stick insects, etc.), nerve‐dependent differentiation (Orthoptera), regenerating limbs (Amphibia, Crustacea, stick* insects, etc.), late‐fertilized Amphibian eggs, graft‐tolerant sites (cheek pouches of hamster), crown‐gall tumours and other plant galls, and toadstools. The rate of development of spontaneous and induced tumours is related to size of species. Further investigation is needed to determine (a) if this holds also for size of breed, (b) if it is related to rate of development to maturity, or to length of life. Crown‐gall tumours in plants are initiated by a bacterium, Agrobacterium tumefaciens, which induces an irreversible alteration in the plant's tissue leading to high heteroauxin production and unorganized tumorous growth. Plant tissues cultivated for long periods on media of high auxin content acquire many properties of crown‐gall tumour tissue. Desoxyribonucleic acid extracts from A. tumefaciens can transform other species of bacteria so that they induce tumours. Virus tumours in plants are induced by a combination of a specific virus and traumatic injury. Some tumours are determined genetically, with high or complete penetrance, either as a result of gross genetic imbalance in species crosses (Nicotiana, Platy‐poecilus, Pygdera), or of chromosomal imbalance (extra B‐chromosomes in Sorghum pollen‐grain tumours) or of single genes or systems of genes (Drosophila larval melanotic tumours, melanomas in grey horses, human xeroderma pigmentosum, tumour incidence in monozygotic twins, some mammary cancers and leukaemias in mice). The incidence (penetrance) of genetic tumours may vary markedly with diet and other environmental conditions (notably in Drosophila), with stage of development (all Drosophila tumours regress at metamorphosis), and with genetic background (notably in different inbred mouse strains, which show marked differences of proneness to various tumours). Some single genes affect cancer‐proneness, e.g. yellow in mice increases the incidence of lung cancer, and the A blood‐group allele in man that of gastric cancer. Specific, subspecific and breed differences in cancer spectrum or particular cancer‐proneness must have a genetic basis; human ‘racial’ differences may do so, but may be determined by environment or habits. The incidence of some mammary cancers in mice depends on a combination of genetic factors with a virus transmitted in the milk. Incidence is mediated through the timing of the endocrine‐dependent mammary cycle, high incidence occurring in strains where local areas of proliferation persist after the rest of the gland is in regression. Histocompatibility genes determine susceptibility to tumour transplantation, but have no relation to genetic cancer‐proneness. The study of ascites tumours has revealed a wide genetic variance in the cell populations of tumours, due to polyploidy, aneuploidy, structural changes (notably translocations) and gene mutations. The tumour is propagated mainly through a ‘germplasm’ of modal'stem cells’, the remaining more extreme variants constituting its non‐transmitted ‘soma’. In changed conditions, selection may operate to alter the profile (idiogram) of the variance, with the establishment of a new mode and set of stem cells (e.g. hypertetraploid in place of hyperdiploid). Major physiological adaptation of the entire cell population is not operative. Immunoselection results in new aneuploid modes with loss of antigenic properties. In other conditions, selection of other mutants may result in higher proliferation rate or invasiveness. Inbred mouse strains may change their general or particular cancer‐proneness, as a result of deliberate or unconscious selection. Thus, though the abnormal ploidies and structural changes often seen in tumours are certainly not the primary cause of tumorigenesis but secondary effects of it, they may provide the basis for further genetic evolution of the tumour. The apparent lack of any marked ‘heredity’ of cancer in man and wild animal species is due to (a) the multiplicity of types of cancer, and (b) the genetic heterogeneity of natural populations. Whenever inbreeding is practised, breeds or strains with particular degrees of genetic proneness to particular cancers will be established. The high variance of human populations in genetic cancer‐proneness accounts for the fact that very high incidence of known occupational, environmental or habitudi‐nal cancer will only occur with very prolonged and very intense exposure to the carcinogen. Lesser degrees of exposure will result only in a moderate incidence, which yet may be causally significant, as with the increase of lung cancer due to cigarette smoking. Evolutionary selection may affect the manifestation and incidence of cancers in various ways. It may operate (a) to produce a relative immunity to tumorigenesis in tissues especially subject to environmental insults, e.g. the nasal mucosa; (b) to defer the onset of reasonably common cancers, such as most carcinomas, to post‐reproductive ages; this will not be possible with rare cancers such as most sarcomas, or with cancers with very early onset, such as the leukaemias of childhood, or xeroderma pigmentosum; in this latter case selection has produced an alternative mode of palliation, by imposing recessiveness on the deleterious effects of the gene responsible. Cancers are also subject to a general orthoselective pressure in favour of higher proliferation rate and greater invasiveness.

This publication has 80 references indexed in Scilit: