Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins. VI. Radiation.
The following is an attempt to devise a theory of specific induction processes required of the neoplastic transformation using the non-specific carcinogenic agent - radiation. A variety of biological considerations including comparative radiosensitivity, radiation effects on chromatin and enzymes, radiomimetic chemical induction of chromosomal anomalies, lethality and the tRNA function are also presented. These topics serve as background for elaborating a scheme of how a specific array of genes could become decontrolled. A concept derived involves the fixation of despiralized genic areas which are induced by hypomethylated DNA caused by anomalous DNA methylation. This process could be a potentially critical part of the irradiation-induced carcinogenic event. The concept of fixation of chromatin in an informational sense leads to a mechanism requiring a classic mutation, modified by a repair process that ultimately leads to an epigenetic event. More specifically it would appear that a critical target to induce the neoplastic response from a cell with irradiation could be the DNA responsible for the template sites (or at least a secondary area that indirectly could cause inactivation of this site) of the genes for DNA methylation. This would not necessarily be the only genic change required but one can derive gene derepressions from this type of molecular lesion. A similar scheme for gene repression has not been devised in this writing beyond the simplistic, although not unwarranted, viewpoint of direct DNA damage.
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D002843:Chromatin / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004798:Enzymes / Q000528:radiation effects; D004926:Escherichia coli / Q000528:radiation effects; D006801:Humans; D008466:Mechlorethamine / Q000494:pharmacology; D008962:Models, Theoretical; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D012343:RNA, Transfer / Q000528:radiation effects
D002273:Carcinogens; D002843:Chromatin; D004798:Enzymes; D008466:Mechlorethamine; D012343:RNA, Transfer