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If the chemical causes cancer via a mutagenic
mode-of-action three basic predictions exist:
- The frequency of induced mutations per target tissue
will be higher than the frequency of tumors per target tissue.
- Mutations will be observed prior to the observation of
tumors (temporal relationship).
- If a chemical is a mutagenic carcinogen, mutations
should be induced at doses lower than those required to form tumors
(dose-response).
Preliminary collaborative work between NCTR (led by Martha
Moore, Bob Heflich and Ralph Kodell) and Bruce Allen and Annette Shipp of
Environ has found promising results for distinguishing the role of mutagenesis
in carcinogenicity by chemicals that are mutagens (as defined by a series of
genotoxicity/mutagenicity tests) and carcinogens, but which may or may not have
mutation as their primary mode of carcinogenic action. Better consideration of
the impact of mutagenicity in the mode of action of these types of carcinogens
would put cancer risk assessment, linear or not, on a firmer foundation.
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