Here is a new and unique view of carcinogenesis. It will take
you into cellular territories off the usual beaten cancer research
track of cancer mutagenesis. It will require that you view and
read carefully, and with an open mind, the many pages in this
website. This is a new idea. No other cancer research has
explored the basis of carcinogenesis via molecular modeling.
However, at this particular time, there is no cure for cancer,
so new ideas for its cause and cure must come forth.
This website has been
developed to encourage students and
researchers to consider
studying and pursuing this concept and
to consider re-testing
and then re-evaluating the compounds for
human trials.
Illustrated by Simeon C. Daugherty and Valerie L. Pense
Website development by Jim Kershner
Do you have cancer? If you have cancer, the cancer cells in your body are replicating (duplicating) uncontrollably and are invading normal tissue in your body. This study indicates that replication of the cancer cell is out of control; and, to cure cancer, control must be re-established. This 50-year cancer study indicates that the uncontrolled replication of the cancer cell is caused not by a mutation but by a lesion (a chemical bond alteration) within a DNA structure called the TATA box . The lesion is determined via molecular modeling to reside in one of the TATA nucleotides , the thymine (T). According to the author's study, this particular TATA box with its lesion is located in the DNA genome site where replication begins called the replication origin . As determined in the author's study, the lesion locks the on-off switch (that arrangement of elements within the box) into its activation (on) phase. Thus, replication cannot turn off, and the cell completely loses regulatory control over replication. Immediately following this regulatory aberration, many DNA nucleotide triplet-coded adjustments ( mutations ) begin to occur and are involved in the cancer development process to keep the cancer cell alive. Accordingly, this lesion in DNA is presented in this study as the primary event in the development of cancer; and, if cancer is to be cured, this lesion must be removed.
What precisely is this chemical bond lesion? This chemical bond lesion inside the chemical structure of the TATA box converts the normal chemical bonds of three oxygen and two carbon atoms into a single-bonded chemical structure called an ozonide. As viewed in this study, these normal chemical bonds can be converted into an ozonide by radiation energy, by a particular virus, or by various hazardous chemical species.
Precisely where is this ozonide located in DNA? According to the study, the ozonide is located within a section of one of the thymine nucleotides of a TATA box. Specifically, the ozonide is located in the nucleoside (the base and sugar structures of the nucleotide) of the affected thymine nucleotide. According to the study, the ozonide is produced – via radiation energy, for example – within the bent part of the TATA box during the bending of the box by the TATA box protein (TBP) during normal DNA replication. Thus, the more frequent the normal replication -- and thus the more frequent the bending of the TATA box -- the greater is the opportunity for production of the lesion. It is well known that increased normal cell replication during growth in children makes them more susceptible to radiation energy absorption (in the frequently bending TATA box) and thus to development of cancer.
How can a cancer be cured? Cancer can be cured by removing this lesion, the ozonide, from the TATA box and thus returning the regulatory TATA box back to its normal activating-deactivating (on-off) replication function.
How can this lesion be removed? Three potential therapeutic compounds have been designed by the author as a result of the study. The compounds were synthesized and laboratory-tested (in three separate prominent laboratories) and have had dramatic success killing cancer cells ( in vitro and in vivo ) in the laboratory research. The compounds are called Compound B, Compound K , and Compound Z. The compounds were designed precisely to reach the lesion and to remove it by dissociating its chemical bonds. The compounds are neither cancer vaccines nor cancer preventive agents. In early laboratory research, these compounds displayed efficacious results in various cancer cells and in mice affected with cancer. However, additional laboratory testing, including human trials, is required for these unique compounds. To protect the proposed treatment and the compounds, the author was awarded a patent No. 6,294,678 entitled Treatment for Cancer and Compounds for Use therewith .
How did all this come about? This study was begun on April 8, 1957 by biophysicist George P. Sakalosky, Ph.D. in an effort to find the primary event in DNA that causes cancer. He is the author of this presentation and will continue to be referred to herein as the author . Using molecular modeling during the study, the author revealed that a critical energy-absorption site exists in a TATA box in DNA where, in that site, a cancer-initiating lesion can be produced during normal cell replication. According to the modeling results, the lesion would activate replication in an explosive-like manner, and this uncontrolled replication would initiate and promote development of the cancer cell. The author claims that, according to the results of the study, without the presence of the ozonide lesion in that particular TATA box, there is no cancer. And, of course, as the final step in the study, the author designed, as noted above, three somewhat similar compounds, any one of which is designed to reach the site of the lesion, remove the lesion, and thus stop the replication of the cancer cell and cause its demise.
What were the author's molecular modeling tools? In 1957, the author began development of the tools required for the study: the Periodic Symmetry Concept and the Symmetry Analytical Model (SAM). These two molecular modeling tools, in addition to serving the study, became the basis of the author's doctoral thesis, entitled Proton Symmetry: Its Implications for Learning Theory – a Biophysics Concept. This thesis followed the completion of interdisciplinary, intercollegiate, doctoral courses at MIT; at Tufts University School of Medicine; at Boston University ; and at Boston College where, in 1975, the author was awarded a doctoral degree.
Can these compounds also kill HIV? A cancer laboratory researcher at the M.D. Anderson Cancer Center in Houston, Texas, where he was testing the compounds for their effectiveness against various types of cancer cells, discovered that two of the compounds -- Compound K and Compound Z -- had unusual properties and suggested that they be tested against HIV. The compounds were transported to an HIV laboratory where they tested positive against HIV. These efficacious HIV results by the compounds indicated that because the compounds apparently removed the lesion in cancer cells (the cancer cells were killed), the HIV was also being killed because it was using the same type of cancer-producing lesion, the ozonide , for its own replication purposes, and the lesion was being removed by the compounds. The need for a lesion to activate the replication of HIV was determined by the research of Zmudzka and Beer, HIV researchers in the Radiation Biology Branch of the FDA, who reported, in 1990, their research conclusion, as follows: “These observations suggest that specific types of molecular lesions [in DNA] are needed to activate HIV.” However, they did not identify any particular lesion in their research. Because of their unusual properties, these compounds might thus be useful in serving as potential therapeutic agents for both cancer and AIDS.
How do the results in this molecular modeling study relate to other research? Many of the observations in the author's study regarding the lesion are consistent with technical views reported by notable scientists and notable cancer researchers. For example, reporting their research in 1999, Drs. Thoma and Aboussekhra, at the Institute for Cell Biology, Zurich , Switzerland , said “We demonstrated that TBP is sufficient in vivo and in vitro to generate [via ultraviolet radiation energy] a specific DNA lesion (6-4PP) within the bent part of the TATA box.” Their research supports the fact that a particular lesion can be produced in the TATA box by ultraviolet radiation energy absorbed within the bent part of the box when the TBP bends the box during normal cell replication. However, they do not identify the ozonide lesion in their research.
How does this concept via molecular modeling conclude? The ozonide, as noted and as identified via this study, occupies a critical deactivation site in the TATA box and thus activates cell replication dramatically. The ozonide, because of its properties, can, during cell replication, readily replicate itself in the TATA box via autoxidation from the T in the mother DNA strand (on one side of the box) to the T in the daughter strand (on the other side of the box) and thus continue its presence from one cell to another in the living system. By this unique means, this particular lesion, the ozonide , can be considered as a self-replicating, on-going, life-threatening, energy product in DNA, with the cancer cell using this lesion as its driving force.
How might you view this complex concept illustratively in a concise manner? The following illustrations provide a brief, simplified, and concise view of the important features of the author's study. The origin of the technical details related to the ideas in these illustrations will be provided in the various major categories listed in this website.
Fig. 1. The TATA box containing eight complementary nucleotides bonded into two DNA strands, mother and daughter, located in the helical structure of DNA.
Fig. 2. The TATA box located at the beginning of a gene in DNA and serving as a key regulatory unit by participating in the activation of transcription of the gene (or the activation of replication of the genome).
Fig. 3. The Symmetry Analytical Model (SAM) developed on the basis of the rules in the Periodic Symmetry Concept , both developed by the author for the purpose of identifying the primary carcinogenic chemical bond lesion in DNA.
Fig. 5. The TATA Box Protein (TBP) bends the TATA box 100 degrees during the process of transcription or replication, but the bend occurs only momentarily. By means of the bending, the three double bonds become aligned momentarily and, at that instant, can absorb energy to produce a single-bonded lesion, the ozonide. The bending produces an open window to energy absorption in the nucleoside of the TATA box.
Fig. 6. An increased replication rate can readily increase the rate of the alignments and thus increase the possibility of producing a lesion in the nucleoside. Whenever the bonds are aligned continuously during increased rates of replication , the window is opened continuously, thus continuously increasing the possibility of energy absorption and bond conversion, by radiation, chemical, or virus, to produce a single-bonded lesion.
Fig. 7. A lesion can readily be produced when double bonds and their pi electrons are aligned. This is known to occur during the alignment of two carbon-carbon double bonds between two adjacent thymine nucleotides in DNA, producing a lesion called the thymine dimer . When the alignment occurs as above, the lesion produced is called an ozonide.
Fig. 8. The production of an ozonide by the well known chemical reaction called ozonolysis requires an initial alignment of energy-absorbing double bonds and a source of energy impacting the pi electrons of the bonds.
Fig. 9. The ozonide with its various characteristics and properties lies within the thymine nucleoside of the TATA box. This lesion is considered by the author as the primary carcinogenic chemical bond lesion in DNA.
Fig. 10. This illustration shows the details of the locked-on feature of the constituents of the TATA box in the presence of the ozonide, as determined via molecular modeling. As shown, the TATA box cannot turn off when the ozonide is present and thus produces autonomous replication of the cell.
Fig. 11. By means of autoxidation , the ozonide located in one strand of the DNA helix can reproduce itself in the adjacent strand. Thus, the ozonide in the mother strand can reproduce itself in the daughter strand, thus passing the lesion onto a subsequent cell and rapidly moving it throughout the organ and, by metastasis, throughout the entire body.
Fig. 12. It is known that certain mutations increase the rate of replication, thus increasing the open window rate to provide greater opportunity for energy absorption and ozonide production in the TATA box.
Fig. 13. A photo and depiction of a normal and cancerous cervical cell showing the high nuclear/cytoplasmic ratio and other irregularities in the cancer cell (bottom) as compared with the normal cervical cell (top), both taken in Pap smears which were analyzed to determine the presence of cervical cancer. The cervical cancer cell will reproduce itself dramatically. Dr. Hahn of the Dana-Farber Cancer Institute describes the reproduction of a tumor cell as follows: "If you look at most solid tumors in adults, it looks like someone set off a bomb in the nucleus".
Fig. 14. This is a representation of the replication origin in the genome of the cell and is the depicted and most likely location of the critical cancer-causing energy-absorption site (the nucleoside in the TATA box) and the origin of the replication of the cancer cell.
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