PubMed1983
In recent years with all sophisticated incoming data, it has become obvious that "cancer" is indeed a cellular disease. This level of biological organization is extremely pivotal, because it is at this level that the interactive control mechanisms have failed, rendering excessive proliferation and uncoordinated growth, which persists after cessation of the stimuli which evoked it. Although we are extremely interested in identifying and describing the stimuli (etiology), presently as toxicologic pathologists, we are called upon in rendering a diagnosis as to whether given findings are "cancer", and by extension whether an administered substance has caused these findings in laboratory animal species. For some time now the etiology has been confused with the diagnosis and the identification of the causative stimuli with the manifested effects. Although we don't know yet the entire story about the etiology of the oncogenic process we can say that we know a lot about its manifestations and therefore we are capable of making the diagnosis. By virtue of our training, we are capable of identifying, classifying and describing all oncogenic manifestations, no matter whether they are in mice or men. In the course of this pursuit we need some order. Oncogenesis is a multistep, multistage process. We must therefore have a design capable of describing and differentiating initiation, potentiation, promotion, modification, and autonomy in our laboratory animal studies. We must also address the status of the biological resistance of the animal organism through pertinent comparative correlations. Furthermore, since "cancer" is a disease, and a syndrome, we must not limit ourselves in studying only the incidence of a single manifestation in an animal, especially if we intend to use it in extrapolation, but the entire multiplicity of manifestations. In biology, in order to effectively extrapolate, we need appropriate changes in the orders of magnitude. The new chemical entity should be compared structurally to the known human and rodent oncogenic substances. The interspecies differences in toxicokinetics and metabolism compared and the type and location of target cell, as well as, the extent of genetic distortions should be established. By implementing all these it is possible not only to render an accurate diagnosis but also estimate the human "cancer" risk.