A comparison of 5-fluorouracil metabolism in human colorectal cancer and colon mucosa
Article Abstract:
Like many drugs, 5-fluorouracil (5-FU) is not directly responsible for its therapeutic effects. Rather, 5-FU is converted by cellular enzymes into other biochemical compounds which actually accomplish the desired effects. 5-FU is a cytotoxic drug; that is, the drug is poisonous to cells and is used in the chemotherapeutic treatment of cancer. As is the case with all chemotherapeutic agents, it is toxic to both normal and cancerous cells, and the success of the chemotherapeutic treatment relies on greater susceptibility of the rapidly dividing cancer cells. The cytotoxic actions of 5-FU appear to stem from its metabolic conversion into two related compounds, 5-fluoro-uridine-5'-triphosphate (FUTP) and 5-fluoro-2'deoxyuridine-5'-monophosphate (FdUMP). FUTP may interfere with normal cellular metabolism by becoming incorporated into cellular RNA, while FdUMP inhibits the enzyme thymidylate synthetase (TS), which plays a key role in the synthesis of new DNA. Before being converted into either of these two compounds, 5-FU must be converted into a metabolic intermediate called FUMP. A study was conducted to measure the metabolic conversion of 5-FU into these compounds in both normal colon tissues and in specimens of colorectal cancer. The tissues for the biochemical measurements were surgical specimens obtained from patients with colorectal cancer. The enzymes which convert the 5-FU were found to be about three times more active in the cancerous tissues than in the healthy specimens. This difference in enzyme activities may account for the preferential antitumor effect of 5-FU. However, colorectal cancer is not one of the cancers more susceptible to 5-FU treatment. It may be possible to improve the susceptibility of this cancer to 5-FU by enhancing the metabolic factors which facilitate the conversion of 5-FU to FUMP. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Cancer
Subject: Health
ISSN: 0008-543X
Year: 1991
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Repair processes in the treatment and induction of cancer with radiation
Article Abstract:
The author was awarded the 1989 Charles F. Kettering Prize, sponsored by the General Motors Cancer Research Foundation. At a series of lectures honoring the prizewinners, Dr. Elkind reviewed his work. Although living cells had been grown in culture around the turn of the century, it was not until the 1950s that cell culture came into its own as a practical avenue of research. Dr. Elkind applied this new field to the study of radiation damage, a subject of growing interest in the brand-new nuclear age. He and his colleagues found that the tissue culture cells had a remarkable ability to repair the damage to radiation, and proposed a theoretical framework for the evaluation of lethal doses of radiation. Briefly, Elkind assumed that a lethal dose of radiation, for a cell, meant the accumulation of sublethal damage until a threshold had been crossed. This could be theoretically deduced by examining the shape of the survival rate-radiation dose curve. It could be experimentally confirmed by examining the effects of fractionated doses, i.e. doses of radiation given over a period of time rather than all at once. The apparent lethal dosage would be altered by the amount of repair that the cell could accomplish between doses; this is precisely what was observed. Fractionated lethal doses were consistently larger than a lethal dose given all at once. Radiation is both a cause of cancer and a destroyer of cancerous tissue. The useful dose is limited to the point at which it begins to destroy normal tissue in addition to the cancer. Although an understanding of the repair mechanisms at work is far from complete, such understanding is important for the improvement of cancer treatment protocols. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Cancer
Subject: Health
ISSN: 0008-543X
Year: 1990
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