IUBio

Dose Response

Chuck Miller rellim at MAILHOST.TCS.TULANE.EDU
Sat May 1 13:41:39 EST 1999


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J. Smith wrote...
I agree. The problem, however, becomes more complicated with "threshold"
carcinogens because they have little measurable effect on DNA (not known =
to
cause mutation). These epigenetic genetic carcinogens include compounds =
like
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) which the US EPA =
claims is
one of the most potent carcinogens known to man. TCDD is not known to =
cause
mutation in several bacterial, yeast or mammalian test systems and is =
thought
to act to promote previously initiated cells (always present) through =
receptor
mediated pathways to form tumors.


Would you suggest another set of biological markers of "threshold" based =
events
that can be said to be "promotional" in nature as useful markers of =
epigenetic
carcinogen action? Such a proposal would have to encompass the fact that
chemicals known to promote cancer progression can be dependent on not =
only the
dose applied, but also to the time and frequency of application as well =
as
route and tissue specificity.

And in reply...

I think there is probably a set of biomarkers (e.g., C to T changes that =
arise from 5-meC deamination) that would be common in tumors that arise =
from treatments with promoter/progressors like acetaminophen, TCDD, =
carbon tetrachloride, etc.

I have never understood why such a "potent" carcinogen like TCDD has =
such a weak epidemiological record of disease associated with exposures. =
You would think that if the dioxin family was so deadly that there would =
be cancers, etc., popping up all over the Seveso and Viet Nam =
populations.

A study just published from this state surveyed the population and found =
that the residents believed that environmental exposures to pollutants =
and pesticides caused as much disease as smoking. This misperception =
persists despite the work of real epidemiologists like Doll and Peto, =
who reported ~ 20y ago that environmental exposures contribute very =
lttle to cancer incidence. Bumping TCDD up to a "known human carcinogen" =
has just increased fear and confused matters, and has not helped public =
health. One day the government(s) will get it right and stop subsidizing =
tobacco farming and getting people to eat less. This would cut out ~80% =
of the cancers as well as cut arthritis, cardiovascular diseases, =
premature aging, etc.=20

Chuck

 =20


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<DIV><FONT color=3D#000000 size=3D2>J. Smith wrote...</FONT></DIV>
<DIV><FONT color=3D#000000 size=3D2>
<P>I agree. The problem, however, becomes more complicated with=20
&quot;threshold&quot;<BR>carcinogens because they have little measurable =
effect=20
on DNA (not known to<BR>cause mutation). These epigenetic genetic =
carcinogens=20
include compounds like<BR>2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or =
dioxin)=20
which the US EPA claims is<BR>one of the most potent carcinogens known =
to man.=20
TCDD is not known to cause<BR>mutation in several bacterial, yeast or =
mammalian=20
test systems and is thought<BR>to act to promote previously initiated =
cells=20
(always present) through receptor<BR>mediated pathways to form =
tumors.<BR>
<P>Would you suggest another set of biological markers of =
&quot;threshold&quot;=20
based events<BR>that can be said to be &quot;promotional&quot; in nature =
as=20
useful markers of epigenetic<BR>carcinogen action? Such a proposal would =
have to=20
encompass the fact that<BR>chemicals known to promote cancer progression =
can be=20
dependent on not only the<BR>dose applied, but also to the time and =
frequency of=20
application as well as<BR>route and tissue specificity.</P>
<P>And in reply...</P>
<P>I think there is probably a set of biomarkers (e.g., C to T changes =
that=20
arise from 5-meC deamination) that would be common in tumors that arise =
from=20
treatments with promoter/progressors like acetaminophen, TCDD, carbon=20
tetrachloride, etc.</P>
<P>I have never understood why such a &quot;potent&quot; carcinogen like =
TCDD=20
has such a weak epidemiological record of disease associated with =
exposures. You=20
would think that if the dioxin family was so deadly that there would be =
cancers,=20
etc., popping up all over the Seveso and Viet Nam populations.</P>
<P>A study just published from this state surveyed the population and =
found that=20
the residents believed that environmental exposures to pollutants and =
pesticides=20
caused as much disease as smoking. This misperception persists despite =
the work=20
of real epidemiologists like Doll and Peto, who reported ~ 20y ago that=20
environmental exposures contribute very lttle to cancer incidence. =
Bumping TCDD=20
up to a &quot;known human carcinogen&quot; has just increased fear and =
confused=20
matters, and has not helped public health. One day the government(s) =
will get it=20
right and stop subsidizing tobacco farming and getting people to eat =
less. This=20
would cut out ~80% of the cancers as well as cut arthritis, =
cardiovascular=20
diseases, premature aging, etc.&nbsp;</P>
<P>Chuck</P>
<P>&nbsp; </P></FONT></DIV></BODY></HTML>

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