Ask A Scientist Chemistry Archive

(Created prior to 1993)

Question: What are the chemical reasons that some molecules are carcinogenic 
and others are not?
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Mutations in DNA are what causes cancer.  Nitrous acid (HNO2) is 
an example of a mutagen.  It will modify cytosine, adenine, and guanine in the 
DNA through a process called oxidative deamination.  An amine group (C-NH2) is 
converted to a carbonyl group (C=O).  So cytosine will be converted to uracil.  
Uracil pair with adenine, which in turn pairs with tyrosine.  As DNA 
replicates, these pairings are thrown off right from the start (which is bad) 
and so cancerous cells with mutated DNA are formed.  Another example is the 
known carcinogen benzene.  Once in the body, enzymes in the liver (called 
P450's, I think) us use the oxygen from the heme group in hemoglobin and make 
an epoxide on the benzene ring (an epoxide is an oxygen bridged between two 
carbons).  This new molecule can either form or act as a free radical (look it 
up) and alkylate the DNA bases (alkylate is to add carbon chains to other 
molecules) I have already mentioned the consequences of modified DNA above 
agents is fairly high compared to radiation mutagens (like UV light and X
rays).  Humans can withstand a fair amount of chemical mutagens before 
mutations start whereas once radiation hits the cell mutations occur 
instantly.  Lung cancer from asbestos will not show up for years while skin 
cancer from too much sun shows up considerably sooner 
Joe Schultz
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Fascinating!  Good answer Joe!  So, just to break it down a 
little, it sounds like the one thing carcinogens have in common is that they 
have the ability to make subtle mutations of DNA.  After all, the oxidative 
deamination you mentioned does not have much in common with the alkylation of 
bases via free radical reactions.  SO, is it possible to answer the original 
question simply, i.e., are there simple chemical rules which determine which 
compounds are carcinogenic and which ones are not?  I would guess that the 
answer is no, and that although we have learned a lot in recent years about 
various mutagens, we are still (scientifically speaking) at a stage where we 
are identifying new carcinogens from scratch.  However, I guess that any free 
radicals in the bloodstream would be potential carcinogens, as well as 
anything which can convert amines to carbonyls . . . however, I am a little 
confused about one thing.  I always thought that nitrous acid in solution made 
nitrosonium ions (NO+) which react with primary amines to form nitrosoamines 
(R-N-N=O), and that nitrosoamines were carcinogenic in small quantities.  Is 
my chemistry off here?  It has been a LONG time since I took organic.  Maybe 
there are subsequent reactions which make a carbonyl out of the nitrosoamine?  
I just do not know.
Topper
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Your chemistry is not off, Robert.  It would be easier to show 
the mechanism but imagine this.  After the nitrosoamine is formed, there is an 
H-shift to form a diazoalcohol (I think that is what it would be called).  The 
OH is protonated and water is split off leaving a diazo cation.  N2 comes off 
leaving a cation for water to attack producing a phenol-like structure (I am 
talking about cytosine now).  Another H-shift takes place leaving a carbonyl 
and a protonated N adjacent to the carbonyl . . . uracil.  I had to draw it 
out to convince myself!  P.S.  I knew that biochem degree would do me some 
good!
Joe Schultz
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