Carcinogenic mechanisms: a critical review and a suggestion that oncogenesis may be adaptive ontogenesis.
The precise mechanism(s) whereby normal cells become malignant are not known with any degree of certainty. However, many mechanisms have been proposed on the basis of available experimental evidence as interpreted by the proposer. These fall into two main groups and are based upon changes in genetic structure (somatic mutation hypotheses) or in genetic expression (epigenetic hypotheses). Yet a third group embodies elements of the first two. The more important of all these proposals are critically reviewed and yet another hypothesis is ventured. In this hypothesis, the induction of neoplasia is envisaged as embodying (a) initiation of preferentially partly-differentiated and resting stem cells and (b) promotion of the initiated cells, through mitosis and further differentiation and by adaptations of normal ontogenic mechanisms, into a variety of novel phenotypes which are malignant or potentially so. Cancer-specifying genes, altered chromosomes, de-differentiations and interrupted re-differentiations are not considered to be causally involved, although the last three of these can be present as epiphenomena. Evidence cited in support of this proposal appears to show a general absence from cancer cells of any single property, including an abnormality in genetic constitution or in cellular expression, which is specific to malignancy. Malignancy is thus envisaged as abnormal expressions of the genetic potential of the zygote. Some practical and theoretical implications of this concept are discussed.
D000818:Animals; D002273:Carcinogens; D002454:Cell Differentiation; D002875:Chromosomes / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D010641:Phenotype
D002273:Carcinogens