Mutagenicity testing

John Budny jabudny at earthlink.net
Sat Jun 1 23:56:24 EST 1996

Greetings Paul!

You seem to be focused on particle size.  Have you considered the basic 
chemistry of the the two systems you described.  For example do you the 
solubilities of the test material in water and dimethmy sulfoxide?  the 
issue may not be "particle" but rather simply solubility.

Second, during my  "daze" as an industrial toxicologist, I did toxicity 
studies on penetrating aids for dermal delivery of therapeutic agents, 
antiinflammatories, antibiotics (tetracycline), etc.  As I recall, 
particles per se did not cross dermal tissue; rather solubility in the 
penetrating aid was the key issue.  Granted, dermal tissue is not the 
same as mutagenic test system membranes BUT, the test system will not 
likely change the laws of chemistry.

I'll put my money on solubility.  Can you get, say three or four 
materials with diverse solubilities in water and DMSO and correlate the 
relative mutagenic indexes as a function of solubility?

Interesting problem.  Please keep me - us posted.


Jack Budny
jabudny at earthlink.net

p.whitehead at dial.pipex.com (Paul Whitehead) wrote:
>Clearly, assessment of mutagenic (genotoxic) potential of a chemical
>in in vitro screens relies on cell uptake of the chemical in question.
>Does anybody have any information concerning the effect of particle
>size on cell uptake, particularly with regard to chromosomal
>aberration assays (CHO or human lymphocytes) and the Ames test?
>For example, is there a limit below which particles will be taken up
>into the cells even if the test substance is presented as an aqueous
>suspension rather than a solution in an organic solvent?  Conversely,
>what, if any, is the upper particle size limit whereby such material
>will be excluded thus rendering the assays meaningless?
>This is a relevant subject since I have the results of several in
>vitro assays with negative results where an aqueous suspension was
>tested, but positive results when the same (dried) material was
>dissolved in eg DMSO.  I am trying to conclude whether this is an
>aberration(!) of the test system or that testing of the aqueous
>suspensions was meaningless.  Particle size distribution is known for
>the materials.
>Thanks for any help or pointers to relevant information sources.
>Paul Whitehead BSc CBiol MIBiol DABT
>United Kingdom
>e-mail p.whitehead at dial.pipex.com

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