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Molecules and Cancer
Name: Unknown
Status: N/A
Age: N/A
Location: N/A
Country: N/A
Date: Before 1993
Question:
What are the chemical reasons that some molecules are carcinogenic
and others are not?
Replies:
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
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
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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Update: June 2012
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