Natural products, carcinogenicity

Some enviromnental agents are carcinogenic tobacco, coal tar, asbestos, alcohol, some polycyclic aromatic hydrocarbons. X-rays and other sources of radiation, and many natural products. 

Electron-rich alkenes are the more reactive jr-bond snbstrates towards epoxidation by the electrophilic dioxiranes Some typical examples of these oxidations are snm-marized in Scheme 2. Since the resnlting epoxides are nsnally hydrolytically and ther-molytically qnite labile, snch oxidations are best carried ont with isolated dioxiranes. For example, the 8,9 epoxide of the well-known aflatoxin B, postnlated as potent carcinogen in the oxidative metabolism of this natural product, escaped numerous efforts to prepare it by conventional epoxidations because of its sensitivity towards hydrolysis . The synthesis of this labile epoxide was readily accomplished by employing a solution of the isolated DMD at room temperature (equation 2), and its mutagenicity unequivocally... 

Some natural products, or their degradation products, represent a hazard for mammals not because of general toxicity but for subtle, adverse properties, such as carcinogenicity and tumor promotion. They are best known fi om marine dinoflagellates (okadaic acid and structural analogues), filamentous fungi (trichothecenes and ochratoxins), and plants (pyrrolizidine alkaloids). 

Ethidium is a model compound for these studies. In human pharmacology, two classes of natural products (actinomyces, anthracyclines) provide prototypic molecules as DNA intercalating agents. (Planar molecules tend to insert well into the stacked nucleic acids, which accounts for the carcinogenic potential of polyaromatic hydrocarbons see figure 7.5.)... 

The natural-occurring carcinogen cycasin, which is a glycoside of methylazoxymethanol (Fig. 1.1), is hydrolyzed by the gut bacteria after oral administration. The product of the hydrolysis is methylazoxymethanol, which is absorbed from the gut and which is the compound responsible for the carcinogenicity. Given by other routes, cycasin is not carcinogenic, as it is not hydrolyzed. 

A few other comments Ethanol is listed by OSHA as a suspect but unproved carcinogen, but OSHA does not have jurisdiction over beverage alcohol, nor, since it is a natural product, does the Delaney Amendment apply. This could lead to paradoxical situations. Ethanol will continue to grow explosively in volume in the next few years as a motor fuel indeed, this has happened in Brazil. The field is extremely volatile, and new developments occur every week, particularly with respect to fermentation and gasohol. Things should be clearer in about five years, and we should remind ourselves to take a similar look at ethanol then. 

Benzene Petroleum, coal tar, trimerization of acetylene, natural products, etc. Colourless liquid, b.p.80°C m.p.5.5°C. stable. Has relatively pleasant odour, (carcinogenic). Industrially a very important compound). 

Bartsch H. Gefahrliche Naturprodukte sind Karzinogene im Krautertee [Hazardous natural products. Are there carcinogens in herbal teas ] MMW Fortschr Med 2002 144(41) 14. 

Rosenkranz HS, Liu M, Cunningham A, Klopman G. Application of structural concepts to evaluate the potential carcinogenicity of natural products. SAR QSAR Environ Res 5(2) 79-98, 1996. 

If we expand our notions of environmental chemicals to include natural components of the diet, we might then begin to see why it is of great importance to continue to study their health effects. Diet, as we have seen in Chapter 7, importantly contributes to human cancer rates. We do not understand a great deal about why this is, but it is surely far more complex than the rate and form of our fat and fiber intakes. Perhaps industrial products are not the major human carcinogens, but natural products may well be. To make matters more complicated, it is also apparent that many natural dietary constituents protect against certain cancers. Indeed, some may increase the risks of certain cancers and reduce that of others It is not unexpected that some industrial chemicals will be shown to have these same properties. 

Ishikawa, T., Takayama, S., Kitagawa, T., et al., In vivo experiments of trptophan pyrolysis products, in Naturally Occurring Carcinogens-Mutagens and Modulators of Carcinogenesis, Miller, E. C., Miller, I., Hirono, T., et al., Eds., University Park, Baltimore, MD, 1979, 159-167. 

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