Abstract:
:The Benchmark Dose (BMD) method is the favored approach for quantitative dose-response analysis where uncertainty measurements are delineated between the upper (BMDU) and lower (BMDL) confidence bounds, or confidence intervals (CIs). Little has been published on the accurate interpretation of uncertainty measurements for potency comparative analyses between different test conditions. We highlight this by revisiting a previously published comparative in vitro genotoxicity dataset for human lymphoblastoid TK6 cells that were exposed to each of 10 clastogens in the presence and absence (+/-) of low concentration (0.25%) S9, and scored for p53, γH2AX and Relative Nuclei Count (RNC) responses at two timepoints (Tian et al., 2020). The researchers utilized BMD point estimates in potency comparative analysis between S9 treatment conditions. Here we highlight a shortcoming that the use of BMD point estimates can mischaracterize potency differences between systems. We reanalyzed the dose responses by BMD modeling using PROAST v69.1. We used the resulting BMDL and BMDU metrics to calculate "S9 potency ratio confidence intervals" that compare the relative potency of compounds +/- S9 as more statistically robust metrics for comparative potency measurements compared to BMD point estimate ratios. We performed unsupervised hierarchical clustering that identified four S9-dependent groupings: high and low-level potentiation, no effect, and diminution. This work demonstrates the importance of using BMD uncertainty measurements in potency comparative analyses between test conditions. Irrespective of the source of the data, we propose a stepwise approach when performing BMD modeling in comparative potency analyses between test conditions.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Wheeldon RP,Dertinger SD,Bryce SM,Bemis JC,Johnson GEdoi
10.1002/em.22422subject
Has Abstractpub_date
2021-01-11 00:00:00eissn
0893-6692issn
1098-2280pub_type
杂志文章abstract::Amoxicillin (AMO), a drug used in the treatment of infections caused by susceptible bacteria, has been evaluated for its ability to induce genotoxicity in human peripheral blood lymphocytes. The potential genotoxic effects of AMO were investigated in vitro by the sister chromatid exchange (SCE), chromosomal aberration...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20531
更新日期:2010-04-01 00:00:00
abstract::A set of stable nitroxide free radicals that are used as spin labels have been shown to possess metal-independent superoxide dismutase-like activity. Unlike superoxide dismutase (SOD), these compounds are low molecular weight, and readily penetrate into the cell. A representative nitroxide, 4-hydroxy-2,2,6,6-tetrameth...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850190105
更新日期:1992-01-01 00:00:00
abstract::To what extent noncovalent chemical-DNA interactions, in particular weak nonbonded DNA intercalation, contribute to genotoxic responses in mammalian cells has not been fully elucidated. Moreover, with the exception of predominantly flat, multiple-fused-ring structures, our ability to predict intercalation ability of n...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20036
更新日期:2004-01-01 00:00:00
abstract::The 1960s witnessed detailed studies on the genetic properties of a large number of histidine-requiring mutants of Salmonella typhimurium. The early 1970s saw development of selected strains, the Ames strains, for use in rapid, cheap, sensitive, and manipulable tests of chemicals and chemical mixtures for genotoxic ac...
journal_title:Environmental and molecular mutagenesis
pub_type: 历史文章,杂志文章
doi:10.1002/em.2850140610
更新日期:1989-01-01 00:00:00
abstract::The L5178Y mouse lymphoma cell mutagenesis assay is used to detect the mutagenic activity of chemicals in a mammalian cell system. To evaluate this assay we compared the results of assays performed independently on 63 chemicals by laboratories at SRI International and Litton Bionetics, Inc. The two laboratories used s...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2860120506
更新日期:1988-01-01 00:00:00
abstract::Two freshwater species of planarians, Girardia schubarti Marcus and G. tigrina Girard, were used for measuring chromosome aberration (CA) induction under laboratory conditions. Three genotoxicants were tested: methyl methanesulfonate (MMS), a direct-acting genotoxicant; cyclophosphamide, a metabolism-dependent genotox...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20307
更新日期:2007-07-01 00:00:00
abstract::Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The intera...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22113
更新日期:2018-01-01 00:00:00
abstract::The mutagenic activity of airborne particulate matter collected in Pisa, a small nonindustrial town located in Italy, has been monitored over 1 year using the Ames Salmonella Test. Airborne particulate was collected on fibreglass filters using a Hi-Vol sampler and extracted by sonication and Soxhlet acetone extraction...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850130306
更新日期:1989-01-01 00:00:00
abstract::The acquisition of breast ductal fluid by nipple aspiration and ductal lavage are simple noninvasive procedures to sample breast tissue. Nipple aspiration fluid (NAF) obtained with gentle suction and a simple syringe-adapted apparatus may evaluate the secretory components that bathe the ductal epithelial cells. Evalua...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.10061
更新日期:2002-01-01 00:00:00
abstract::Lead is a widely existing environmental pollutant with potential carcinogenicity. To investigate the association of blood lead level (B-Pb) with potential chromosomal damage and cancer, we analyzed micronucleus (MN) frequency of peripheral blood lymphocytes (PBLs) and the methylation status of six human tumor suppress...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22194
更新日期:2018-07-01 00:00:00
abstract::AQ-13 ([N1-(7-chloro-quinolin-4yl)-3-(N3,N3-diethylamino)propylamine] dihydrochloride trihydrate) is an aminoquinoline antimalarial drug that is effective against chloroquine-resistant strains of Plasmodium falciparum. It is structurally similar to the widely used chloroquine diphosphate (CQ). We evaluated these drugs...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.1052
更新日期:2001-01-01 00:00:00
abstract::Human sulfotransferase (SULT) 1A1, 1A2, and 1A3 cDNA genes were subcloned separately into the pTrc99A(KM) vector. The generated plasmids were introduced into the Salmonella typhimurium O-acetyltransferase-deficient strain NM6000 (TA1538/1,8-DNP/pSK1002), resulting in the new strains NM7001, NM7002, and NM7003. We comp...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20696
更新日期:2012-03-01 00:00:00
abstract::Human lymphocytes and Chinese hamster ovary (CHO) fibroblasts were analyzed for cytogenetic and cytotoxic endpoints to determine whether exposure to power frequency (60 Hz) electromagnetic fields (EMF) interferes with normal cell growth and reproduction. An exposure chamber was built to apply variable electric current...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850170108
更新日期:1991-01-01 00:00:00
abstract::Black cohosh extract (BCE) is a popular botanical dietary supplement marketed to relieve symptoms of various gynecological ailments. Studies conducted by the National Toxicology Program (NTP) showed that BCE induces micronucleated erythrocytes in female rats and mice. Subsequently, the NTP showed that a variety of BCE...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22334
更新日期:2019-12-01 00:00:00
abstract::Male Swiss mice are tested under uniform 50-Hz electric field intensities of 100, 170, 220, and 290 kV/m. These values on the basis of equal induced current density are equivalent to the case of a human exposed to field intensities of nearly 8, 14, 18, and 24 kV/m, respectively. The latter values may be found beneath ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850130204
更新日期:1989-01-01 00:00:00
abstract::We have applied the alkaline comet assay to study the functional impact of gene polymorphisms in base excision repair (APEX1 Asp148Glu, XRCC1 Arg194Trp, XRCC1 Arg399Gln) and homologous recombination repair (XRCC3 Thr241Met, NBS1 Glu185Gln), two pathways that play crucial roles in the repair of DNA damage induced by me...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20415
更新日期:2008-12-01 00:00:00
abstract::The genotoxic effects associated with automobile painting were analyzed using a panel of biomarkers. Chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronuclei were evaluated in 25 car painters (12 smokers, 13 nonsmokers) working in different automobile paint-shops in Italy and in 37 control subje...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20147
更新日期:2005-10-01 00:00:00
abstract::311 chemicals were tested under code, for mutagenicity, in Salmonella typhimurium; 35 of the chemicals were tested more than once in the same or different laboratories. The tests were conducted using a preincubation protocol in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclo...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850190603
更新日期:1992-01-01 00:00:00
abstract::Exposure to emissions from laser printers during the printing process is commonplace worldwide, both in the home and workplace environment. In the present study, cytotoxic and genotoxic effects of the emission from five low to medium-throughput laser printers were investigated with respect to the release of ozone (O(3...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20695
更新日期:2012-03-01 00:00:00
abstract::The genotoxic responses of mixtures of four chlorohydroxyfuranones (CHFs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA), 3-chloro- 4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), were compared with the geno...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20017
更新日期:2004-01-01 00:00:00
abstract::DAS (diallyl sulfide), DADS (diallyl disulfide), and DATS (diallyl trisulfide) are major oil-soluble allyl sulfides (OAS) that represent major garlic constituents. The anticarcinogenic and antimutagenic effects of these substances have been extensively studied during the last decades. Previous reports suggest that ind...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20467
更新日期:2009-04-01 00:00:00
abstract::Combinations of antiretroviral drugs that include nucleoside reverse transcriptase inhibitors (NRTIs) are superior to single-agent regimens in treating or preventing HIV infection, but the potential long-term health hazards of these treatments in humans are uncertain. In earlier studies, our group found that coexposur...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10073
更新日期:2002-01-01 00:00:00
abstract::Molindone hydrochloride is a dihydroindolone neuroleptic with dopamine D2 and D5 receptor antagonist activity. As an integral component of its preclinical safety evaluation, molindone hydrochloride was evaluated in a series of in vitro and in vivo genetic toxicology assays. In the bacterial reverse gene mutation assay...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22007
更新日期:2016-05-01 00:00:00
abstract::Comparison of spontaneous mutation spectra derived from different transgenic constructs can provide valuable insights for interpreting the mechanisms of spontaneous mutation. In this study, spontaneous mutation frequencies and spectra of the lacI transgene are compared in the liver of C57BL/6, B6C3F1, and BC-1 mice an...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.1021
更新日期:2001-01-01 00:00:00
abstract::The phenoxyherbicide and peroxisome proliferator 2-methyl-4-chlorophenoxyacetic acid (MCPA) was tested for its ability to induce sister-chromatid exchanges (SCE) in chick embryos. Erbitox E30 (a commercial formulation containing 28% MCPA sodium potassium salt as active ingredient) was injected into the air chamber in ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850190411
更新日期:1992-01-01 00:00:00
abstract::Evidence is provided that antitopoisomerase drugs induce chromosomal aberrations via the formation of DNA double strand breaks. Camptothecin, an inhibitor of DNA topoisomerase I, produced only chromatid-type aberrations, and in order to be effective it has to be present during the DNA replication. The fact that it ind...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.2850220416
更新日期:1993-01-01 00:00:00
abstract::Exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water was associated with an increased incidence of oral tumors in F344 rats in a 2-year cancer bioassay conducted by the National Toxicology Program. These tumors primarily occurred at 180 ppm Cr(VI) and appeared to originate from the gingiva...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21952
更新日期:2015-08-01 00:00:00
abstract::Antioxidant vitamins are able to deactivate highly bioactive molecules, such as free radicals, that are generated during cellular biochemical processes. Doxorubicin (DXR) is a cancer chemotherapeutic agent that generates free radicals as a byproduct. In the present study, the Drosophila melanogaster somatic wing spot ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20160
更新日期:2006-01-01 00:00:00
abstract::Benzo(a)pyrene (BaP) is a mutagenic carcinogen that is ubiquitous in our environment. To better understand the toxic effects of BaP and to explore the relationship between toxicity and toxicogenomics profiles, we assessed global mRNA and microRNA (miRNA) expression in Muta™Mouse. Adult male mice were exposed by oral g...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20668
更新日期:2012-01-01 00:00:00
abstract::DNA damage and its subsequent repair occur heterogeneously throughout the genome, which reflects the nature of the damaging agents, gross chromosomal structure, the specific nucleotide sequence, and transcriptional status. We selected to investigate the repair of DNA damage in an artificial, transgenic situation. Here...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00