Carcinogenicity of aromatic compounds

[Allen Smith]

In article <009593F1.30B0890C.10723 at NTDOC.NCTNET.GOV>, wmelchior at NTDOC.NCTNET.GO
   V ("Bill Melchior, NCTR/FDA") writes:
>>      I've received a few letters and have seen a brief discussion
>>      without any sort of resolution on the rumour I posted sbout
>>      DMAE, it's solvent and cancer.  A reader contacted twinlabs
>>      (tm) and stated the nervous operator shakily confirmed that
>>      the only solvent that they used with their DMAE was water.
>>
>>      I recently found a DMAE bottle in a healthfood store and
>>      found the DMAE in TWinlabs to be in  a PABA (para-amino ben-
>>      zoic acid) base.  The solvent is indeed water.
>>
>>      So I checked out the biomed libraries' reports on PABA.  I
>>      found a few reports of similar substances being
>>      carcinogenic.  I'm an amateur and I don't have these
>>      articles handy, but I believe these were pyrridines.  I
>>      found Peter Alex the med student on the shuttle today and
>>      he suggested the benzoic acid was the problem.  He
>>      said that it is hypothesized that benzene itself is the
>>      culprit in causing cancer.  We talked a little about the
>>      chemical structure and the floating electrons of the
>>      benzene ring and the efficacy of this structure in fucking
>>      with DNA replication.  Benzene is the same thing responsible
>>      for the potent carcinogenic activities of burnt barbeque
>>      meterial which is basically just a clump of benzene riings.
>>
>>      The journals were mostly unreadable to this novice but
>>      by the availability of benzocaine, sunscreens containing
>>      benzene-type chemicals (which react with UV light to create
>>      free raqdicals) that this issue is either unresolved or
>>      not yet critical (as the journals seemed to suggest- in-
>>      conclusive.)  PATMS (peter alex the med student) believed
>>      the necessity of these products in medical practices
>>         currently outweighs their dangers.  This didn't make sense
>>      to me, aS the use in suncreen is to PREVENT cancer while
>>      he claimed these same substances CAUSED cancer.
>
>
> Although the carcinogenicity of aromatic hydrocarbons is not my field,
> perhaps I can shed some light on this problem.
>
> First, there is a big difference between benzene, C6H6, and the much
> larger "polycyclic aromatic hydrocarbons" ("PAH"s), which have multiple
> rings joined together along their edges.  The mechanisms by which PAHs
> damage DNA have been extensively studied.  Such damage depends on
> metabolism of the compounds to oxidized species which can react with
> groups on the DNA.  The degree of metabolism, first, and the amount and
> type of damage to DNA, second, depend on several details of the
> structure of the molecule, such as the geometric layout of the rings
> and the presence of other side chains attached to the rings.  The DNA
> damage, with resulting mutations and tumor formation, are well characterized.
>
> Benzene, on the other hand, has been associated with leukemia, but
> experimental studies are mostly lacking.  This means that the interaction
> with DNA is not well characterized, either as to the nature of the
> reacting compound or the type of the resulting damage.  Oxidation has been
> proposed as playing a role here, also, but benzene is much less reactive
> than PAHs, so experiments are less informative.
>
> A couple of points should be kept in mind.  1)  The majority of chemicals that
> react with DNA do so after being metabolized -- changed into more reactive
> compounds -- by enzymes in the body.  2)  Caution is needed in proposing
> that a chemical may cause cancer merely because an apparently similar one
> does; simply moving methyl group from one place to another on a molecule
> may change its carcinogenecity by orders of magnitude.  (Remember that common
> salt, NaCl, is made up of sodium and chlorine atoms.  Both sodium and chlorine
> are dangerous in their elemental state, but NaCl is not only harmless in
> reasonable amounts, but absolutely vital to life.)  Thus it is totally
> wrong to say something like
>>       Benzene is the same thing responsible
>>      for the potent carcinogenic activities of burnt barbeque
>>      meterial which is basically just a clump of benzene rings.
>
> ______________________________________________________________________________
   __
> The opinions stated are mine, not those of NCTR or its sponsoring organization
   s.
>
> Bill Melchior                                ||   Evolution, as described in
> National Center for Toxicological Research   ||   J. A. Paulos' _Innumeracy_:
> Jefferson, AR  72079                         ||
> (501) 543-7206                               ||  "Eventually, primitive life
>                                              ||   develops, and then shopping
> wmelchior at ntdoc.nctnet.gov                   ||   malls."

        I thought I'd repost this to alt.drugs, since the original query
came from there. It's somewhat unsurprising that Bill didn't leave the
cross-postings where they were; NCTR (so far as I can tell) is sponsored
by the FDA.
        -Allen