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Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
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OCR for page 27
4
SUMMARY AND CONCLU SION S
The Committee' second assignment was to determine the
feasibility of studying the quantitative value of short-term
mutagenicity tests for prediction of carcinogenicity. Having
reviewed this topic, the Committee does not believe that the
Na tional Research Council should conduct a more detailed ~ tudy
now .
There is no doubt that short-term mutagenicity tests, such
as the Ames Salmonella/microsome test, have been successful in
identifying carcinogens. A substance that is found to be muta-
genic in such a tes t is clearly a possible human carcinogen.
This is attested by the very high fraction of known carcinogens
that are positive in short-term mutagenicity tests arid by the
large number of mutagens that were f ire t detected by short-term
tests and later found to be positive in animal cancer tests.
The difficulty lies in the question of whether such tests can
be used for quantitative prediction of human carcinogenicity.
The Committee believes that such tests may well have quanti-
tative utility, but that it would be premature to make con-
clusive statements now. Rather than calling for the judgment
of a National Research Council study, the situation calls for
more research and analys is of data.
The relation between an initiating event, which may well be
mutation, and the eventual development of a cancer is complex
and is thought to involve multiple steps. Thus, the prediction
of care inogenicity is more complex than the prediction of DNA
damage iteel f . The activation systems used in short-term
mutagenicity tests may not parallel those involved in human
carcinogenesis, particularly those related to promotion and
proliferation. Furthermore, some carcinogens are not detected
in short-term mutagenicity tests. Until these discrepancies
are resolved and more data have been analyzed, a National
Research Council study will not be justified. This is not to
say that we must wait for certainty; that would be the path to
inac t ion. Bu t we be 1 ieve the t s tud ie s now in progres s may we
provide much better information..
27
OCR for page 28
Large studies have been started by Ames et al.50 and
McCann_ al.S6~74 and by GENE-TOX. All involve analysis of
large bodies of data, and a part-time National Research Council
group would not have the facilities for such analysis. We
believe that, if a National Research Council assessment is
needed, the proper time to undertake it would be when the large
analyses now going on are completed.
In conclusion, the Committee on Chemical Environmental
Mutagens thinks that it is not now feasible for the National
Research Council to study the use of short-term mutagenicity
tests for quantitative prediction of human carcinogenicity.
Whereas the data are sufficient to establish a firm qualitative
association, current models would require additional verifica-
tion and study to make them sufficient for quantitative pre-
diction. We recommend that the outcome of the several large
projects that are in progress be awaited before consideration
of a National Research Council study.
*
28
Representative terms from entire chapter:
mutagenicity tests
