Short-term tests for carcinogens and mutagens

Hollstein, Monica; McCann, Joyce; Angelosanto, Frank A.; Nichols, Warren W.

doi:10.1016/0165-1110(79)90014-9

Cited by 484 publications

(77 citation statements)

References 413 publications

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“…Since such biological reactions indicate DNA damage, they can be useful in detecting carcinogenic and mutagenic effects (Hollstein et al, 1979;Zeiger, 1998).…”

Section: Introductionmentioning

confidence: 99%

Induction of mitotic crossing-over in diploid strains of Aspergillus nidulans using low-dose X-rays

Stoll

Crémonesi²,

Pires³

et al. 2008

Genet. Mol. Res.

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ABSTRACT. As a contribution towards detecting the genetic effects of low doses of genotoxic physical agents, this paper deals with the consequences of low-dose X-rays in the Aspergillus nidulans genome. The irradiation doses studied were those commonly used in dental clinics (1-5 cGy). Even very low doses promoted increased mitotic crossing-over frequencies in diploid strains heterozygous for several genetic markers including the ones involved in DNA repair and recombination mechanisms. Genetic markers of several heterozygous strains were individu- ally analyzed disclosing that some markers were especially sensitive to the treatments. These markers should be chosen as bio-indicators in the homozygotization index assay to better detect the recombinogenic/ carcinogenic genomic effects of low-dose X-rays.

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“…Since such biological reactions indicate DNA damage, they can be useful in detecting carcinogenic and mutagenic effects (Hollstein et al, 1979;Zeiger, 1998).…”

Section: Introductionmentioning

confidence: 99%

Induction of mitotic crossing-over in diploid strains of Aspergillus nidulans using low-dose X-rays

Stoll

Crémonesi²,

Pires³

et al. 2008

Genet. Mol. Res.

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“…Cu ions injected into the ascites, tumour were found to be present in the DNA double helix structure (Agarwal et al 1990). Cu compounds have been also found to be genotoxic in animal cells in culture (Flessel 1978, Hollstein et al 1979. However, similar results were not observed in bacterial colorimetric assay the SOS chromotest (Olivier and Marzin 1987).…”

Section: Resultsmentioning

confidence: 51%

Potential Genotoxicity in Copper Sulphate Treated Mice.

Fahmy

2000

CYTOLOGIA

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“…This list is not exhaustive and the degree to which these tests have been validated varies widely. comparability with carcinogenicity data obtained in vivo (59,60 The test systems considered either incorporate some aspects of mammalian metabolism, e.g., by adding a microsomal fraction of rodent or human liver in vitro or by using metabolically competent rodent cells, or involve activation in vivo, as in the host-mediated assay in intact mammalian organisms and in the test in Drosophila melanogaster (Table 3). Because of its efficiency, low cost and rapidity, the Salmonella/microsome test has been used most extensively; it therefore also has been most extensively validated, and 30 identified and suspected human carcinogens have been assayed (Tables 4 and 5 Of the possible human carcinogens (Table 5), amitrole, carbon tetrachloride and polychlorinated Table 3; classification refers to test systems grouped in Table 3.…”

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confidence: 99%

Comparison between Carcinogenicity and Mutagenicity Based on Chemicals Evaluated in the IARC Monographs

Bartsch¹,

Tomatis²

1983

Environmental Health Perspectives

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The qualitative relationship between carcinogenicity and mutagenicity (DNA-damaging activity), based on chemicals which are known to be or suspected of being carcinogenic to man and/or to experimental animals, is analyzed using 532 chemicals evaluated in Volumes 1-25 of the IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. About 40 compounds (industrial processes) were found to be either definitely or probably carcinogenic to man, and 130 chemicals have been adequately tested in rodents and most of them also in various short-term assays. For a comparison between the carcinogenicity of a chemical and its behavior in short-term tests, systems were selected that have a value for predicting carcinogenicity. These were divided into mutagenicity in (A) the S. typhimurium/microsome assay, (B) other submammalian systems and (C) cultured mammalian cells; (D) chromosomal abnormalities in mammalian cells; (E) DNA damage and repair; (F) cell transformation (or altered growth properties) in vitro.The following conclusions can be drawn. In the absence of studies in man, long-term animal tests are still today the only ones capable of providing evidence of the carcinogenic effect of a chemical. The development and application of an appropriate combination of short-term tests (despite current limitations) can significantly contribute to the prediction/confirmation of the carcinogenic effects of chemicals in animals/man. Confidence in positive tests results is increased when they are confirmed in multiple short-term tests using nonrepetitive end points and different activation systems. Assays to detect carcinogens which do not act via electrophiles (promoters) need to be developed. The results of a given short-term test should be interpreted in the context of other toxicological data. Increasing demand for quantitative carcinogenicity data requires further examination of whether or not there is a quantitative relationship between the potency of a carcinogen in experimental animals/man, and its genotoxic activity in short-term tests. At present, such a relationship is not sufficiently established for it to be used for the prediction of the carcinogenic potency of new compounds.There is increasing evidence to suggest that DNA damage (expressed mainly as mutations) is involved in the induction of many cancers; however, the relevance of the various biological end points used in short-term assays to mechanisms of tumor induction is not known precisely. All test procedures must therefore be validated before they can be used to predict the carcinogenicity of chemicals. Ideally, such validations would be based on correlations between responses in short-term tests and data from epidemiological studies in humans.

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Short-term tests for carcinogens and mutagens

Cited by 484 publications

References 413 publications

Induction of mitotic crossing-over in diploid strains of Aspergillus nidulans using low-dose X-rays

Induction of mitotic crossing-over in diploid strains of Aspergillus nidulans using low-dose X-rays

Potential Genotoxicity in Copper Sulphate Treated Mice.

Comparison between Carcinogenicity and Mutagenicity Based on Chemicals Evaluated in the IARC Monographs

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