U Scientists Isolate P-450, Cancer-Cause Fighter

A team'of biochemists at :.he University Medical Cenlter has isolated a red protein substance (cytochrome P-450) from liver that filters out environmental pollutants and helps detoxify harmful drugs !and certain cancer-causing agents. P-450, a colored cell, does not cure cáncer any more than ït rids the air of carbon monoxide. But it does help the body oxidize and excrete such as petroleum products, chemicals, drugs (including marijuana and nicotine), even alcohol. The team was led by Dr. Minor J. Coon, professor and chairman of the U-M department of biochemistry, and his 'associates. The associates, whom Coon gives full credit, include Drs. Anthony Lu, Henry Strogel, Anne Autor and Miss Joanne Heidema. The U-M scientists did not discover P-450; two Japanese scientists did. But the U-M investigators are the first to succeed in separating the protein from liver raembranes. Their efforts were reported to an international symposium on drug metabolism sponsored by the Swedish Medical Council and will also be pres e n t e d this month at a symposium i n Edinburgh, Scotland, sponsored by the British Biochemical Society. P-450 is a little known red protein, or pigment, that accelerates the metabolism of hormones, fatty acids and other chemicals and foreign substances required by the body. Coon and bis fellow biochemists cali it "the most versatile biological catalyst known." One of Prof. Coon's students calis P-450, "Miraculase," not only because it works miraculously but also because it is a unique catalyst which both speeds up oxidation of chemicals essential to human life and detoxifies poisonous substances that man inhales and ingests. As a catalyst it accomplishes in the body in the presence of oxygen what outside might require the equivalent power of a pneumatic hammer or the intense heat of a fíame thrower. Without P-450, according to Coon, people would not even be able to tolérate scch simple medications as aspirin, let alone such violent combinations as barbiturates and alcohol. It is a scientific anomaly, as it is both an activator and an antidote. P-450 is also fragüe. It took Dr. Coon and his associates two years just to learn how to stabUize and extract the red protein. "It was like breaking a light bulb to study light," said Coon. "When you break up liver membranes you risk losing the very chemical reactions you hope to study." When the U-M scientists did succeed, they found another tiny but significant piece of the puzzle of the life process. Dr. Coon feels that biochemists and physicians w i 1 1 soon have for the first time "a rational basis for chemotherapy." He means that now a patient's tolerance to l ful medications and risky chemicals can be studied and measured during the course of j treatment "It may take years of technical refinement, but in time we should be able to do a simple liver biopsy with a syringe, extract P-450, analyze it, and advise physicians what Chemicals, singly or in combination, the patiënt can tolérate," he said. "We expect our work ultimately to help physicians understand and better control what are now admittedly unpredictable combinations of medications," Dr. Coon said. Now the way is open to biochemists and phamacologists, and eventually physicians, to predict the effects and duration of drugs- not merely the addictive and harmful variety but those required for the treatment of. disease, including cáncer. P-450 in the liver (Dr. Coon calis the liver biochemically -- - - - "The most important organ in the body") oxidizes and makes soluble noxious substances that are increasingly polluting the environment. P-450 also makes it possible for the kidneys to excrete the potentially poisonous pollutants. On the Iatter issue, pollution, Dr. Goon is conservative but hopeful. It is, he believes, unlikely that bottles of P-450 will soon be found on medical shelves to be given to residents of heavily polluted areas. At present in its natural form, the substance is too large a molecule to get into liver cells by external means. But the U - M scientist believes that the liver is the site and P-450 is the secret to part of the solution to pollution. He suggests that the challenge is now to make a low molecular weight ie substitute for natural P-450 so that it can be absorbed by the liver and thereby inerease its efficiency. "What we need to do now is to duplicate the active site, or the business end, of P-450 in such a way that it will enter liver cells and not be rejected or excreted as some kind of transplanted, foreign substance," suggests Coon. Because the U-M biochemist does not believe civilization will return to the relatively free, unpolluted 19th century, he urges more basic research on the liver as a detoxifier. "We've got to find ways of pepping up the liver and helping it do a better job of detoxification, because we can't wait around for it to I adapt by an evolutionary J process to an increasingly 1 hostile atmosphere," Dr.l Coon states. I