Use of computerized data listings and activity profiles of genetic and related effects in the review of 195 compounds

Waters, Michael D.; Stack, H.Frank; Brady, Ann L.; Lohman, P.H.M.; Haroun, L.A.; Vainio, Harri

doi:10.1016/0165-1218(88)90024-9

Cited by 83 publications

(32 citation statements)

References 26 publications

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“…In addition, animal studies have shown that after benzene exposure, increases in micronuclei, chromosome loss, and breakage are seen in the hematopoietic cells of mice and rats (1,4,5). These chromosomal effects, combined with observations that benzene is only weakly mutagenic in standard gene mutation assays (6,7) and binds poorly to DNA (8,9) suggest that indirect genetic mechanisms that result in translocations, deletions, aberrant recombination, or aneuploidy may be important in benzene's genotoxic effects (10,11). It is also likely that the chromosome damage seen in the blood cells of occupationally exposed populations reflects alterations occurring in the hematopoietic stem cells, which contribute to leukemogenesis.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of human topoisomerase II in vitro by bioactive benzene metabolites.

Frantz

Chen

Eastmond

1996

Environ Health Perspect

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Benzene is a clastogenic and carcinogenic agent that induces acute myelogenous leukemia in humans and multiple types of tumors in animals. Previous research has indicated that benzene must first be metabolized to one or more bioactive species to exert its myelotoxic and genotoxic effects. To better understand the possible role of individual benzene metabolites in the leukemogenic process, as well as to further investigate inhibition of topoisomerase 11 by benzene metabolites, a series of known and putative benzene metabolites, phenol, 4,4'-biphenol, 2,2'-biphenol, hydroquinone, catechol, 1,2,4-benzenetriol, 1,4-benzoquinone, and trans-transmuconaldehyde were tested for inhibitory effects in vitro on the human topoisomerase 11 enzyme. With minor modifications of the standard assay conditions, 1,4-benzoquinone and transtrans-muconaldehyde were shown to be directly inhibitory, whereas all of the phenolic metabolites were shown to inhibit enzymatic activity following bioactivation using a peroxidase activation system. The majority of compounds tested inhibited topoisomerase 11 at concentrations at or below 10 pM. These results confirm and expand upon previous findings from our laboratory and indicate that many of the metabolites of benzene could potentially interfere with topoisomerase 11. Since other inhibitors of topoisomerase 11 have been shown to induce leukemia in humans, inhibition of this enzyme by benzene metabolites may also play a role in the carcinogenic effects of benzene. Environ Health Perspect 104(Suppl 6): 1319-1323 (1996)

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Section: Introductionmentioning

confidence: 99%

Inhibition of human topoisomerase II in vitro by bioactive benzene metabolites.

Frantz

Chen

Eastmond

1996

Environ Health Perspect

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“…In contrast, bioassays can directly indicate the toxicity of a wide range of industrial chemicals (Claxton et al, 1998). More than 200 in vivo assays utilizing insects, plants, and animals are available for identification of toxic chemicals (Waters et al, 1988). However, in vivo tests are more expensive and labor-intensive hence their application for studying industrial wastes have been limited (DeMarini, 1991).…”

Section: Introductionmentioning

confidence: 99%

Toxicity assessment of organic pollutants: Reliability of bioluminescence inhibition assay and univariate QSAR models using freshly prepared Vibrio fischeri

Parvez

Venkataraman

Mukherji

2008

Toxicology in Vitro

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“…The data used in the IARCMonographs on genetic and related effects have been prepared together with the U.S. Environmental Protection Agency (EPA) in the form ofgenetic activity profiles (8,9) The combined utility ofthe information in the IARC databases described here may be even wider than appears from a consideration of each database alone. The whole may be greater than the sum of the parts.…”

Section: Larc/epa Genetic Activity Profilesmentioning

confidence: 99%

Carcinogenicity Evaluations and Ongoing Studies: The IARC Databases

Vainio¹,

Coleman²,

Wilbourn³

1991

Environmental Health Perspectives

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Many thousands ofchemicals are produced industrially and many more occur naturally. Information on the toxicology of these chemicals is often minimal or absent. The International Agency for Research on Cancer (IARC) has published evaluations ofthe carcinogenic risk to humans ofover 700 chemica4 groups ofchemicals, andcompex mixtures as a regular series of monographs. A database has been created containingsummanies ofall the relevant epidemiological, animal carcinogenicity, and other relevant biological data for each chemical or mixture evaluated. Additional databases have been created for ongoing epidemiological studies ofcancer in humans and for long-term carcinogenicity studies in rodents, as well as a database contalning information on genotoxic and related effects ofchemicals. Some ofthese databases have been published in print form. IARC now plans to publish them electronically, together with other databases, in the form of a CDROM (compact disk, read-only memory). The objective will be to make the entire IARC database ofcancer information as widely available as possible in an integrated format conducive to efficient and combined exploitation of all the component databases.

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Use of computerized data listings and activity profiles of genetic and related effects in the review of 195 compounds

Cited by 83 publications

References 26 publications

Inhibition of human topoisomerase II in vitro by bioactive benzene metabolites.

Inhibition of human topoisomerase II in vitro by bioactive benzene metabolites.

Toxicity assessment of organic pollutants: Reliability of bioluminescence inhibition assay and univariate QSAR models using freshly prepared Vibrio fischeri

Carcinogenicity Evaluations and Ongoing Studies: The IARC Databases

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