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Dose-Response

c. miller rellim at MAILHOST.TCS.TULANE.EDU
Thu Apr 29 15:17:49 EST 1999


James Smith wrote...

>I hope to start a detailed discussion about the following:
>
>How does the cancer dose-response for acetaminophen, the active
>ingredient in Tylenol, differ from the cancer dose-response of other
>carcinogens?
>
>Acetaminophen is generally considered safe for human consumption, but
>has been shown in several studies to cause cancer in rats and mice.
>Some scientisits consider acetaminophen to be a carcinogen with a
>threshold. The threshold for acetaminophen carcinogenicity is only
>reached at doses that also cause liver damage. Do we treat
>acetaminophen differently from other carcinogens? And if the answer is
>yes, how do we treat acetaminophen differently under the new US EPA
>Cancer Guidelines?

I agree with you James. There should be an EQUAL and RATIONAL treatment for
all chemicals. I think we need some molecular biology/epidemiology studies
for agents that require significant cytotoxicity to cause cancers. If a
common set of specific mutations in specific genes are found in hepatic
cancers caused by generally "non-genotoxic" agents like acetaminophen,
dichloromethane, etc., then it would support a model in which the outgrowth
of previosly initiated cells is facilitated by cytotoxicity. Such molecular
biomarkers could reveal the actual initiating event and perhaps the
agent(s) that caused the tumor--or at least rule out some possibilities.

Without cell death (a promotion/progression factor) and clonal expansion of
the initiated cells, there would be no chance to form a tumor if these
"carcinogens" have no initiating activity of their own.


Chuck












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