Free Radical Effects -

What's in Cigarette Smoke

Cigarette smoke contains a very nasty mix of free radicals, and some of the thousands of substances present in inhaled smoke and absorbed into the body during smoking, can also produce free radicals. Free radicals bring about many, if not most, of the serious bodily effects associated with smoking, especially the damaging effects on the arteries. Dr. Hermann Ester Bauer, of the University of Graz, Austria, a prominent researcher into the biological effects of free radicals, points out that smoking, a long-recognized risk factor for heart attacks, leads to low-density lipoprotein ( LDL) free radical oxidation , probably from the extra free radicals produced in the body by absorbed smoke ingredients. As we have seen, this is how cholesterol gets deposited in the artery walls, especially in the coronary arteries of the heart.

There is also growing speculation that the cancer risk in smoking may be largely due to free radicals. This speculation is based on some quite strong evidence. Although free radicals are hard to detect directly there are various indirect ways of determining that they have been busy. Protein breakdown products of oxidation can be detected and so can indicators of DNA oxidation damage. When DNA is damaged, it immediately tries to repair itself. This repair work is done by enzymes called 'exonucleases'. When these enzymes get to work they release the compound 8-hydroxydeoxyguanosine. This gets into the blood and is excreted in the urine.

In the December 1992 issue of the scientific journal, Carcinogenesis, which is dedicated to research into the causes of cancer, there is a paper from research scientists at the University of Copenhagen, Arthus University and the Danish Cancer Registry. This paper reports the results of a trail in which the quantities of this tell-tale compound in the urine of smokers is compared with the quantities in non-smokers urine. The figures speak for themselves. The smokers urine contained 50% more 8-hydroxydeoxyguanosine than that of non-smokers. This means that smokers'DNA is suffering a considerably greater rate of damage than that of non-smokers.

This additional damage could be coming either from the free radicals present in cigarette smoke or from free radicals produced in the body. We know that smokers have a higher metabolic rate ( the rate of build up and break down of body bio chemicals) than non-smokers typically 10% to 15% higher. Raised metabolic rate accelerates all kinds of biochemical reaction pathways and some of these produce free radicals.

It would be quite wrong to leave you with the impression that researchers believe that free radicals are the most important cause of smoking induced cancer. There is plenty of evidence that other mechanisms are also at work, especially the effects of the binding to DNA of certain aromatic hydrocarbons found in cigarette smoke. Nevertheless, the current interest in the role of free radicals in this context is intense.

The tell tale indicator of DNA damage in the urine of smokers makes them particularly suitable subjects for investigating whether the antioxidant vitamins C and E can reduce the risk of cancer. Many workers n the field now believe that the time has come for long-term trails of antioxidants. There is, however, one major difficulty. These scientists know better than most what smoking can do to the human body. They therefore have serious ethical reservations about any advance that might encourage smokers to continue. The way to avoid smoking-related body damage is to stop smoking. The scientists are at pains to point out that work of this kind is not done in the hope of trying to make smoking safer.

In addition to the monitoring of urine for 8-hydroxydeoxyguanosine, there are other ways of detecting rates of free radical damage to DNA. Lung cancer is not really cancer of the lung substance itself but of the lining ( the epithelium) of the air tubes ( bronchioles) in the lungs. Bronchial carcinoma the medical term for lung cancer starts in this epithelium. Researchers are, therefore, extremely interested in the epithelial cells that are present in coughed-up sputum. When cell division begins to go wrong an early feature of a change in the direction of cancer short lengths of DNA are left in the fluid within the epithelial cells. These fragments are called 'micronuclei' and the proportion of them is, of course, of great significance.

In a paper in the British Journal of Cancer at the end of 1992, the researcher Geert Van Poppel and colleagues describe how the proportion of micronuclei in epithelial cells coughed up by smokers can be reduced by 30% by taking large doses of the antioxidant, beta carotene.

This result, although of great scientific interest, has alarmed some of the scientists concerned with this problem. The epidemiologist, Professor Richard Peto, FRS, of the Imperial Cancer Research Fund in Oxford, is concerned that news about the value of antioxidants may lead smokers to believe that they can safely continue so long as they take their vitamins. He points out that it is still too early to say that DNA damage by free radicals is the most important reason for the high incidence of cancer in smokers. Whether it proves to be so or not, smoking will remain one of the most dangerous of human activities.