Quantitative Relationship Between Mutagenic and Carcinogenic Potencies A Feasibility Study (1983) / Chapter Skim
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2. The Mutagenicity of Carcinogenic Compounds
2. The Mutagenicity of Carcinogenic Compounds
Pages 8-16
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From page 8... ...
positive results from the Salmonella/microsome test are usually confirmed by other tests, as are negative results and results witch weakly act ive chemicals o f ten conf irmed; and (4 ~ the percentage 8
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58 Ames and McCann6 discussed how the inclusion of questionable carcinogenicity data may influence the interpretation of mutagenicity testing. The accuracy and quantitation of carcinogenicity data are dealt with separately in Chapter 3.
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recently published its 3-year analysis of mutagenicity testing as an approach to carcinogenicity testing. 59 This group concluded that "the uncertainty about the mechanisms by which chemica 1 carcinogens induce cancer precludes the precise selection of predictive tests on the basis of similarities of mechanisms between the test system and the mammalian model of carcinogenesis." Committee 2 cautioned that the expansion of a test battery will produce an increase in false-positive results and thus necessitate the comparison of in vitro data with results of more protracted animal tests, which themselves are uncertain in predicting cancer in man.
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From page 11... ...
He, too, considered mutagenicity tests strictly as qualitative screens for potential care inogenicity. His demonstration of the variability of metabolic activation systems in several human liver extracts argued for a parallel between the variability in the tests and the heterogeneity of the human population in susceptibility to particular chemical carcin' gens.
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From page 12... ...
False~positive or falsenegative mutagenicity results are relative to their agreement with available animal carcinogenicity data, which appear to have a tendency toward fals~negatives. The second recent collaborative study comparing mutagenic ity and care inogenicity results was sponsored by the United Kingdom Environmenta 1 Mutagen Society.
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From page 13... ...
, the UK group recommended that potency be calculated on the basis of the Salmonella/microsome test -- and then only for specif ic bacterial strains . The carcinogenicity results were considered inadequate for deciding whether the consistent negative results accurately described ache activity of the compounds.
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From page 14... ...
In 197B, Purchase and colleaguesl°° determined how well six short-term tests detected carcinogenicity of 120 organic chemica 18: 5 ~ ca rc inogens and 6 2 noncarc inogens from severe functional and structural classes, including polycyclice, alkylating agents, and aromatic amines. Compounds that were negative in studies that extended over most of the animals' lif e span were class if fed as noncarcinogens .
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The noncarc inogens tested included aniline, anthracene, diphenylnitrosamine, and 5-bromo-2 '-deoxyuridine. The high proport ion of fals~positive results precluded quantitative analys i s .
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For the 16 hydrazine derivatives, there was a positive correlation be tween DNA damage and ca rc inogenes i a, bu t no corre let ion between mutagenic and carcinogenic potencies or between mutagenic and DNA-dsmaging activities. In a later study,9b 218 procarcinogens, ultimate carcinogens, and noncarcinogens were compared for their correlation between bacterial mutagenicity and induction of unscheduled DNA synthesis (UDS)
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