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.
jabudny at earthlink.netp.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
>>>Thanks for any help or pointers to relevant information sources.
>>>>Paul Whitehead BSc CBiol MIBiol DABT
>e-mail p.whitehead at dial.pipex.com>