Effects of metals in in vitro bioassays.

Sirover, Michael A.

doi:10.1289/ehp.8140163

Cited by 28 publications

(7 citation statements)

References 74 publications

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“…Cell-free bioassays may be developed as screening systems for indication of metal mutagens/ carcinogens (19,20). This has been demonstrated by the observations of Sirover and Loeb (20,21) and others (22) that mutagenic/carcinogenic metals decrease the fidelity of in vitro DNA synthesis or synthetic polynucleotide templates.…”

Section: Cell-free Systemsmentioning

confidence: 99%

“…Studies of chromosome abnormalities in persons exposed to known or suspected carcinogens, properly controlled for age and characterized for identity, level and duration of exposure, can prove useful for both research and public health purposes (19,28). Studies of chromosome abnormalities in persons exposed to known or suspected carcinogens, properly controlled for age and characterized for identity, level and duration of exposure, can prove useful for both research and public health purposes (19,28).…”

Section: Chromosome Aberrationsmentioning

confidence: 99%

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In vitro Models and Methods for Bioassay and Studies of Cellular Mechanisms

1981

Environmental Health Perspectives

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This report discusses the use of in vitro systems to detect metal carcinogens and to provide inforna-tion on the mechanisms of metal carcinogenesis. The use of in vivo systems is also discussed, where they may provide additional information. Even though no single system has proven adequate for the definitive identification of all metal mutagens and carcinogens, the aggregate results of these studies indicate that the combined use of several systems may provide a valuable, initial screen for metals and their compounds. It is now imperative to evaluate more complex aggregates and mixtures of metals and their compounds that are environmentally ubiquitous (1). Metals appear to behave similarly to other carcinogens in cell transformation tests; however, they are frequently negative in bacterial mutagenesis revertant assays. In addition to rapid screening, cellular systems are particularly advantageous for analyzing the mechanism ofmetal mutagenesis and carcinogenesis. It is only in such systems that one may be able to study the mechanism and specificity of metal-induced cellular alterations which may be causative factors in neoplasia. The physiological chemistry of different metals may vary widely. For example, arsenic and chromium may exist in solution as anions, whereas most other carcinogenic metals exist principally as cations. A major difficulty with metal carcinogens is that no specific metal-nucleic acid interactions analogous to those obtained with organic chemical carcinogens and particular loci in DNA molecules have been observed in vivo. Although recent evidence suggests that most metals do not induce repair synthesis , studies using bacterial or eucaryotic mutants deficient in DNA repair pathways should provide valuable information on metal induced alterations and mechanisms of repair. Furthermore, these cellular assays provide an experimental setting for tracing the involvement of mutations in carcino-genesis. In addition, cell-free systems have permitted measurements of the effects of metals on the fidelity of DNA synthesis with the ultimate goal of analyzing in molecular terms the mechanism of metal carcinogenesis. Conversely, an understanding of metal-cellular interactions should provide new systems to more adequately evaluate the toxic, mutagenic and carcinogenic effects of metals common in our environment. In view of these difficulties and future prospects, recommendations are made in this report and in the commissioned papers to provide more infornation which will lead to an understanding of the mechanisms of metal carcino-genesis. Bacterial Mutagenesis Summary of Present Knowledge To date, bacterial mutagenesis systems have not been successful in predicting the carcinogenicity of 35

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Section: Cell-free Systemsmentioning

confidence: 99%

Section: Chromosome Aberrationsmentioning

confidence: 99%

In vitro Models and Methods for Bioassay and Studies of Cellular Mechanisms

1981

Environmental Health Perspectives

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Section: Cell-free Systemsmentioning

confidence: 99%

“…The metaphase chromosome aberrations produced by metals represent one of the few practical methods currently available for evaluating prior genetic damage in man. The induction of chromosome aberrations by metal compounds has been extensively studied in cultured mammalian cells (4, 19,28). There is a weak correlation between the frequency of chromosome aberrations and the carcinogenicity of metal compounds.…”

Section: Chromosome Aberration Sister-chromatide Exchange and Micronmentioning

confidence: 99%

In Vitro models and methods for bioassay and studies of cellular mechanisms.

1981

Environ Health Perspect

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“…However, beryllium has been shown to induce morphological transformation in mammalian cells and to enhance viral transformation of mammalian cells (48,49). The testing of metals in in vitro assay is reviewed by Sirover (50) in this symposium. Beryllium's ability to decrease the fidelity of DNA synthesis is reviewed in this symposium by Loeb and Zakour (51).…”

mentioning

confidence: 99%

The Carcinogenicity of Beryllium

Kuschner¹

1981

Environmental Health Perspectives

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Effects of metals in in vitro bioassays.

Cited by 28 publications

References 74 publications

In vitro Models and Methods for Bioassay and Studies of Cellular Mechanisms

In vitro Models and Methods for Bioassay and Studies of Cellular Mechanisms

In Vitro models and methods for bioassay and studies of cellular mechanisms.

The Carcinogenicity of Beryllium

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