Another Biological Defense System

Following on from my previous blog article about how do polyaromatic hydrocarbons (PHC’s) like benzo-a-pyrene cause cancer?  It took many years of research by many people to come up with the answer to this question.  Ironically it turns out to be due to a little known biological defense mechanism in our systems that works too efficiently.

Everyone knows about the immune system, that is a complex biological mechanism that recognizes foreign substances in our system and removes them.  This includes bacteria and many chemical substances.  The immune system is so flexible that it can even recognize previously unknown chemicals and remove them from the body.

But, there is a catch, the immune system cannot deal with very hydrophobic substances that are essentially water-insoluble, such a PHC’s.  To remove them from the system (even in very small quantities) another defensive system was developed called the cytochrome P450 system.   This is parallel to but not as widely known as the immune system.  A cytochrome is a protein that is involved in oxygen transfer and cytochrome P450 has a very unusual peak in the UV/vis spectrum, at 450 cm-1 that identifies it.  What this cytochrome does is hydroxylate the aromatic molecule, i.e. it adds an oxygen atom to them that becomes a hydroxyl group to make them soluble and therefore excretable.

But when there is a certain structure of PHC such as benzo-a-pyrene, this system sometimes results in a mistake and in a few percent of cases an epoxide is formed, which contains a very chemically active oxygen.  These planar hydrocarbons being hydrophobic also bind avidly to DNA, they intercalate (insert) between the stacked base pairs.  In doing so, if they are epoxides, they react chemically with the DNA and this leads to mutations and cancer because the DNA cannot be read by the required enzymes.

So this is how chimney sweeps got a special kind of cancer, the PHC’s in the soot, that got into their blood system were expoxylated by the cytochrome P450 system and reacted with the DNA to cause mutations.  Other substances react in a  similar way, for example, the most toxic/mutagenic substance known is aflatoxin.  It is found in the fungus that grows on the inside of the shells of peanuts, and forms a white shiny surface.  This fungus grows very well when the peanuts are stored for long periods in damp conditions.  Nowadays, the storage conditions are kept dry and the amount of aflatoxin is tested and regulated by the FDA in all peanut products, including peanut butter.

Clarification: Please note that there are two distinct uses of the term “aromatic”; in the ordinary meaning to describe a smell such as a perfume, or to describe a series of chemical compounds based on benzene, these two meanings are not synonymous.  The latter compounds can smell and can be highly colored, but not necessarily, and they are not all carcinogenic.