A while back I began to consider that perhaps our models for cancer induction were wrong. Cancer is a disease of uncontrolled clonal expansion or cell division. I was originally taught that this was the result of successive insults to the nuclear DNA in our somatic (differentiated) cells (by largely oxidative events happening over a period of time), which caused them to de-differentiate into more primitive cells, which then lost control of their cell division. The time frame between progressive “transformation” events in this model accounted for the latency between the exposure and the cancer onset. I have since modified my thinking in this regard as new information has come to light.
I no longer believe that somatic cells de-differentiate or that nuclear DNA is the source of the cancer. Instead I believe that cancers originate in pluripotential stem cells and that these cancers can be caused by a single ionization event. The latency can be explained by the long periods of quiescence these stem cells experience during their lifetimes. Is is only when they are stimulated to divide that the clonal expansion goes awry and the cancer manifests itself. I also now believe that radiation damage to other intracellular organelles, such as mitochondria, is likely to be the cause of cancer. Mitochondria are the energy engine of the cell responsible for oxidative phosphorylation. Originally they were free living micro-organisms that eventually formed an intracellular symbiotic relationship with multi-cellular organisms. They were responsible for the huge improvement in energy efficiency from the original anaerobic metabolism through glycolysis (about 4 to 6 ATP molecules per glucose molecule lysed) to around 33 ATPs through, fully oxidized, aerobic metabolism. This improvement in efficiency is achieved by a stepwise drop in the electron potential of oxygen through a cascade of precisely calibrated electron reduction chemical couples, each producing one or more ATPs. I had earlier speculated that radiation damage to the mitochondrion could disrupt this cascade and result in severe oxidative damage to the cell. This is why I considered damage to the mitochondrial DNA to be the source of cancer.
Recently, it has been discovered that mitochondria control cell division, at least at an embryological stage. This insight has been used to cure a form of female infertility through IVF. Mitochondria from a fertile female donor are removed from her donated egg cells and injected into an egg cell from the infertile woman. Her egg cell, with the transplanted “fertile” mitochondria, is implanted into her uterus where the embryo then develops normally. From genealogy we learn that nuclear DNA is inherited in equal parts from our parents; but that the Y-DNA comes only from the father’s sperm and the mitochondrial-DNA (m-DNA) comes only from the mother’s egg. Recently, however, it has been shown that m-DNA segments can be “broadcast” to the brain where they become incorporated in the nuclear DNA of brain cells; so there can apparently be some mixing of m-DNA and nuclear DNA, at least in one direction.