Clearly, if one assumes that promotion involves mitogenesis, then there are multiple ways to cause cells to divide. One can kill cells with both genotoxic and non-genotoxic agents. Stem cells remaining in tissues which have been injured via surgery, burns, viral lysis will be stimulated to go into regenerative hyperplasia. In addition, normal growth [...]
In order to develop a risk assessment model. It is assumed that the model must ultimately be based on a mechanistic understanding of the carcinogenic process. Consequently, it is evident that since we at present do not have complete understanding of the carcinogenic process, any model will be based an current hypotheses and accrued [...]
If all the preceding concepts have some relevance to the understanding of the carcinogenic process, they must somehow be integrated since not one of them can completely explain this complex biological process. In addition, if one ever hopes to develop a biologically-based risk assessment model to predict or explain cancer risks to individuals or [...]
Proto-oncogenes have been defined as sequences of genetic material in a normal cell which appears to function in the regulation of cell proliferation and differentiation. If these genes are mutated, amplified or abnormally expressed, then cell proliferation and/or differentiation would be altered (Weinberg, 1985). These are the hallmarks of a cancer cell; namely, altered proliferation [...]
By phrasing the question in this fashion, one can see that the paradigm to understand the cancer problem is fundamentally wrong. Our current understanding of genetics shapes the concept that DNA, the genetic information, must interact with environmental signals in order to express that information. In other words, the phenotype of an organism is the [...]
One of the important reasons for examining this paradigm is that in considering from whence a cancer cell is derived, two possible answers can be offered: namely, from any one of the hundreds of billions of cells in the body or from only a few special kinds of cells in each organ. Two major theories [...]
With the foregoing as a brief background, an examination of the carcinogenic process in both experimental animals and human beings must be made. The evolution of the neoplastic cell appears to start from a single normal cell, one that obviously has division potential, such as a stem or progenitor cell, which, during the carcinogenic process, [...]
A mutational event is de fined as an alteration in the quality or quantity of genetic information in the cell. In other words, by changing, deleting or duplicating the bases in the DNA molecule (gene) or by changing whole chromosomes or sets of chromosome numbers, the new genetic information in the cell is, for the [...]
How wonderful it would be for both the scientist and policy regulator if, in fact, cancers, in their full-blown form, were “caused” by a single exposure to an agent, which is currently called a “carcinogen”. However, this is naïve, since current experimental cancer studies in rodents (Siaga et al., 1982), in vitro studies with human [...]
Even though mutagenesis by oxygen free radicals has been widely recognized to be a causative factor in the pathogenesis of diseases including cancer, methods for investigating the mechanism for this mutagenesis have not been adequate. Recent advances in molecular biology have allowed one to construct DNA with site-specific modifications identical to those caused by oxygen [...]