Free Radicals as a Possible Cause of Mutations and Cancer 355 



known or suspected to cause cancer. Among these are cigarette smoke, tobacco 

 tars, various other tars, exhaust fumes from cars, smoke from home furnaces 

 or industrial plants, and charred foods. I shall not attempt to cite the literature 

 references for the various evidences that these are carcinogenic agents. It is 

 well known that x-rays and other ionizing radiations can cause genetic mutations 

 and are likewise carcinogenic agents. It is now well known from electron spin 

 resonance that these ionizing radiations also produce radicals which in many 

 biochemical solids (3) (including various proteins, carbohydrates, and fats) 

 persist for long periods after the irradiation. 



The carcinogenic effects of severe chemicals which produce burns of the 

 flesh may possibly result from subsequent diffusion into the healthy cells of 

 free radicals produced in the original, more violent chemical reaction causing 

 the burn. It is known that a burn of the flesh from any source of heat has 

 carcinogenic and mutagenic effects. Since we now know that the charring of any 

 organic matter produces long-lived radicals, it seems probable that some of 

 the carcinogenic and mutagenic effects may result from secondary activity 

 of radicals produced by the burn. Of course chromosome linkages are broken 

 as direct effects of the heat, but it seems probable that most of the cells exposed 

 to the elevated temperatures in the burned area would be killed. 



Certainly many known carcinogenic chemicals are not radicals, and I 

 do not suggest that all cancer may be caused by radicals. However, many 

 chemicals recognized as carcinogenic agents, not themselves radicals, may 

 exert their carcinogenic activity indirectly through the production of radicals 

 within the body. This would be analogous to the indirect effects of ionizing 

 radiations already mentioned and might account for the seemingly parallel 

 action of certain chemicals with ionizing radiations which has led to their being 

 caUed radiomimetic chemicals (5). Many carcinogenic chemicals are large, 

 aromatic, polycyclic hydrocarbons from which it would seem that free radicals 

 might be easily produced. 



The radicals are not convicted from 'guilt by association' with carcinogenic 

 agents. Our proposal is not intended to be accepted per se, but is offered as a 

 working hypothesis which can be put to rather objective test because of the 

 powerful method of electron spin resonance now available for detection of 

 radicals. That certain radicals are likely to be carcinogenic agents, or that 

 some types can lead to genetic mutations, probably will not be questioned. 

 Others, possibly some or all of those which are sufficiently stable in organic 

 matter to be detected with paramagnetic resonance, may be perfectly harmless. 

 I do not therefore recommend that we become suddenly alarmed about the 

 radicals around us. I do think there is some justification for the careful study 

 of these radicals which can be produced, transported, and taken into the body 

 so easily. This study is made easier by the powerful new method of paramagnetic 

 resonance for detection of such radicals. 



If externally produced radicals are indeed dangerous, we can fortunately 

 detect and avoid most of the ones we now are eating, breathing, or rubbing 

 into our skins. Ingram (1) has shown that the number of radicals produced 

 by heating organic matter is a sensitive function of temperature. Tests in our 

 laboratory on common foods such as meat and bread show that those cooked 

 in a normal manner have no detectable resonances or only very weak resonances, 



