Breast Cancer awareness

At the beginning of the 20th century, a link was recognized between certain substances and cancer. In one example, men who were engaged in distilling the bicyclic aromatic substance 2-Naphthylamine later developed cancer of the bladder. Obviously, this substance somehow caused cancer. Such substances were termed "carcinogens".

Many people are afraid of "chemicals", which they suppose to be the most relevant causes of cancer. Yet, this is a misconception. For example, Aflatoxin B1, one of the most relevant carcinogens, is a purely natural product. It is produced by the fungus Aspergillus flavus, which thrives on peanuts, corn, grain or pistachios, if these foods are stored in warm or humid conditions. In many tropical and subtropical parts of the world, this is inevitable for lack of better storage infrastructure. Aflatoxin by itself is not mutagenic. After its ingestion with food, it is taken up via the gut and reaches the liver via the portal vein. In hepatocytes, it is oxidized by the cytochrome P450 enzyme system to a highly reactive intermediate, Aflatoxin-epoxide, which proceeds to bind covalently to nitrogen or oxygen atoms in cellular macromolecules. A typical acceptor in DNA is the N7-atom of guanine. The combination forms a bulky complex termed a DNA adduct. We have efficient repair systems to deal with such adducts, but if the next DNA replication fork comes first, misincorporation may occur. The DNA-aflatoxin-adduct is able to form hydrogen bonds not only with the correct cytosine, but also with adenosine; yet the replication fork seems to get stuck with a C, while it is able to hobble past an A. Altogether, the adduct favors misincorporation of an A. Enter the repair system, which removes the adduct and resynthesizes the strand, placing a T opposite the A. In summary, the process replaces an original G with a T. Likely, this mechanism is responsible for the G→T mutation at the third position of codon 249 of the tumor suppressor p53. This mutation, which is frequently observed in regions burdened by aflatoxin-contaminated food, exchanges Arginine 249 (AGG), which is important for DNA-binding, for a Serine (AGT), inactivating the tumor suppressor. This process is thought to contribute to the high frequency of hepatocellular carcinoma observed in the tropics.

Heating protein-rich food causes numerous chemical reactions. When cooking meats or fish at high temperatures, heterocyclic amines (HCAs) such as  PhiP (2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine) are formed. PhiP causes mutations much like aflatoxin. Oxidation of PhiP's exocyclic amino group by a cytochrome P450 oxidase generates highly reactive N-OH-PhiP, which again reacts with guanine to form a DNA adduct.

In today's society, potential "hidden" environmental carcinogens are the focus of a lot of anxiety. At the same time, people voluntarily expose themselves to established carcinogens all the time: take carcinogens in tobacco smoke or the mutagenic effect of UV irradiation.

16 comments

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