Abstract：
:National and international regulatory agencies historically have used genotoxicity information as part of a weight-of-evidence approach to evaluate potential human carcinogenicity. Additionally, some agencies consider heritable mutation a regulatory endpoint. Furthermore, genotoxicity has the potential to contribute to other adverse health conditions. This article provides a comparative overview of the testing strategies used by regulatory agencies throughout the world. Despite minor variations in details, the genotoxicity test schemes for most regulatory entities generally comprise three tests: a bacterial gene mutation assay, an in vitro mammalian cell assay for gene mutation and/or chromosome aberrations, and often an in vivo assay for chromosomal effects. In some cases, fewer than these three tests are required. In other cases, when exposure data, structure-activity considerations, or other factors warrant, even chemicals negative in the three baseline tests may be subject to additional testing. If genotoxicity is identified by the baseline screening tests, assessment of the ability of the chemical to interact with DNA in the gonad may be required. This may apply regardless of whether or not a cancer bioassay has been triggered. Mutagens positive in second stage gonadal assay(s) may be tested in third stage in vivo rodent tests to provide data for a quantitative risk assessment. In all testing, theutilization of internationally-recognized protocols, where they exist, is advisable, although not in all instances required. When testing for regulatory purposes, it is advisable to verify the testing program with the specific regulatory body or bodies responsible forregulatory oversight before beginning testing.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Cimino MCdoi
10.1002/em.20216subject
Has Abstractpub_date
2006-06-01 00:00:00pages
362-90issue
5eissn
0893-6692issn
1098-2280journal_volume
47pub_type
杂志文章,评审abstract：:Interactions between bleomycin (BLM) and conventional or unconventional intercalating agents were analyzed in an assay for mitotic gene conversion at the trp5 locus and reversion of the ilv1-92 allele in Saccharomyces cerevisiae strain D7. BLM is a potent recombinagen and mutagen in the assay. Various chemicals modula...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.20592
更新日期：2011-03-01 00:00:00
abstract：:This study presents the first application of an in vivo alkaline comet assay using haemocytes of Drosophila melanogaster larvae. These cells, which play a role similar to that of mammalian blood, can be easily obtained and represent an overall exposure of the treated larvae. To validate the assay, we evaluated the res...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.20604
更新日期：2011-03-01 00:00:00
abstract：:Genetic polymorphisms have been reported in several cytochrome P450 (CYP) genes, including CYP1B1 which metabolically activates procarcinogens present in tobacco to carcinogenic intermediates. This study used a case-control approach in North Indian population to determine associations between genetic variants in CYP1B...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.22098
更新日期：2017-07-01 00:00:00
abstract：:Identification of mutations induced by xenotoxins is a common task in the field of genetic toxicology. Mutations are often detected by clonally expanding potential mutant cells and genotyping each viable clone by Sanger sequencing. Such a "clone-by-clone" approach requires significant time and effort, and sometimes is...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.21992
更新日期：2016-03-01 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 in vivo model Drosophila melanogaster was used here to determine the detrimental effects induced by silver nanoparticles (AgNPs) exposure. The main aim was to explore its interaction with the intestinal barrier and the genotoxic effects induced in hemocytes. The observed effects were compared with those obtained b...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.22262
更新日期：2019-04-01 00:00:00
abstract：:Understanding chemically induced changes in mutational spectra can aid in deciphering mechanisms of mutagenesis. In this paper, we propose the use of statistical methods that are based upon the mutation frequency, rather than simple mutant counts which have no relationship to the mutation frequency. These methods have...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/(SICI)1098-2280(1996)28:4<405::AID-EM15>3.
更新日期：1996-01-01 00:00:00
abstract：:DNA damage induced by physical activity and/or exercise has been reported under different conditions but not for individuals maintaining physical fitness by regular strenuous exercise. Therefore, we compared levels of DNA damage in blood leukocytes of 40 healthy individuals (35 males, 5 females) who regularly exercise...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.20457
更新日期：2009-05-01 00:00:00
abstract：:Chlorinated drinking water contains several chlorohydroxyfuranone (CHF) by-products whose contribution to cancer risk is not presently known. 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 studied for th...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.10025
更新日期：2001-01-01 00:00:00
abstract：:DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N-ethyl-N-nitrosourea (ENU) with the persistence of ENU-indu...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.22132
更新日期：2017-10-01 00:00:00
abstract：:Noncovalent DNA interactions, e.g., DNA intercalation and DNA groove-binding, have not been well studied relative to covalent interactions largely due to the inability of predicting and detecting such events in intact cells. We have adapted an in vitro bleomycin amplification method for DNA intercalation for use in cu...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章,评审
doi：10.1002/em.20096
更新日期：2005-03-01 00:00:00
abstract：:Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman Micro...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章,多中心研究
doi：
更新日期：2001-01-01 00:00:00
abstract：:This laboratory has previously described a method for scoring the incidence of rodent blood Pig-a mutant phenotype erythrocytes using immunomagnetic separation in conjunction with flow cytometric analysis (In Vivo MutaFlow®). The current work extends this approach to human blood. The frequencies of CD59- and CD55-nega...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.21924
更新日期：2015-05-01 00:00:00
abstract：:The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Test Procedures held a second harmonization meeting just prior to the U.S. Environmental Mutagen Society Meeting in New Orleans, LA, in April 2000. The discussion focused on several important aspects of the MLA, including: 1) cytoto...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.10122
更新日期：2002-01-01 00:00:00
abstract：:The transporter associated with antigen processing 2 (TAP2) is involved in the development of multidrug resistance and the etiology of immunological diseases. In this study, we investigated whether the expression of TAP2 can be perturbed by single nucleotide polymorphisms (SNPs) located in 3'-untranslated region (3'-U...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.22159
更新日期：2018-03-01 00:00:00
abstract：:The genotoxicity of humic acid and its possible interaction with the herbicides alachlor and maleic hydrazide have been evaluated in cultured human lymphocytes from two donors. Humic acid and the two herbicides have been tested (alone and combined) for sister-chromatid exchange (SCE) induction. In addition, the effect...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/(sici)1098-2280(1997)29:3<272::aid-em7>3.0
更新日期：1997-01-01 00:00:00
abstract：:Iron oxide nanoparticles (ION) with superparamagnetic properties hold great promise for use in various biomedical applications; specific examples include use as contrast agents for magnetic resonance imaging, in targeted drug delivery, and for induced hyperthermia cancer treatments. Increasing potential applications r...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章,评审
doi：10.1002/em.21909
更新日期：2015-03-01 00:00:00
abstract：:A collaborative international trial was conducted to evaluate the reproducibility and transferability of an in vivo mutation assay based on the enumeration of CD59-negative rat erythrocytes, a phenotype that is indicative of Pig-a gene mutation. Fourteen laboratories participated in this study, where anti-CD59-PE, SYT...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.20672
更新日期：2011-12-01 00:00:00
abstract：:Ethylene oxide (EO) is a direct acting alkylating agent; in vitro and in vivo studies indicate that it is both a mutagen and a carcinogen. However, it remains unclear whether the mode of action (MOA) for cancer for EO is a mutagenic MOA, specifically via point mutation. To investigate the MOA for EO-induced mouse lung...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.22080
更新日期：2017-04-01 00:00:00
abstract：:The evaluation of the relationship between the dose to DNA of a mutagen/carcinogen and in vivo somatic cell mutagenesis may provide information on the mechanisms leading to induced mutational events. This can be achieved, for example, by coupling test systems that permit the detection of somatic mutation and recombina...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.2850230304
更新日期：1994-01-01 00:00:00
abstract：:The Pig-a assay is an emerging and promising in vivo method to determine mutagenic potential of chemicals. Since its development in 2008, remarkable progress has been made in harmonizing and characterizing the test procedures, primarily using known mutagenic chemicals. The purpose of the present study was to evaluate ...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.22232
更新日期：2019-01-01 00:00:00
abstract：:Perturbation of DNA replication by chemical-DNA adducts produced by exposure to mutagenic/carcinogenic chemicals results in mutagenic or cytotoxic damage in the DNA. Demonstration of a correlation between cell cycle dependency of cytotoxicity and point mutation at the Na+/K+ ATPase gene could suggest that the two cons...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.2860120304
更新日期：1988-01-01 00:00:00
abstract：:The endogenous X-linked PIG-A gene is involved in the synthesis of glycosyl phosphatidyl inositol (GPI) anchors that tether specific protein markers to the exterior of mammalian cell cytoplasmic membranes. Earlier studies in rodent models indicate that Pig-a mutant red blood cells (RBCs) can be induced in animals trea...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.20667
更新日期：2011-12-01 00:00:00
abstract：:A working group of five statisticians experienced in the use of statistical methods in mutagenicity reviewed aspects of the statistical analysis of genotoxicity test procedures. Issues discussed included methods for integrating biological importance and statistical significance, the relationship of the experimental un...
journal_title：Environmental and molecular mutagenesis
pub_type：
doi：
更新日期：2000-01-01 00:00:00
abstract：:We evaluated the mutagens in fumes produced by heating three different cooking oils used in Taiwan to temperatures of 100 degrees C, 200 degrees C, and 300 degrees C, and constructed models to study the efficacy of fume extractors used commonly by Taiwanese women. Particulates of volatile emissions from lard (at 200 d...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：:Occupational exposure to wood dust is associated with the occurrence of nasal cancer. In this study, we investigated micronuclei and nuclear changes (NCs: binucleates, karyorrhexis, karyolysis, and the "broken egg" effect) in exfoliated buccal cells of 20 workers exposed to wood dust and 20 age- and sex-matched contro...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.20257
更新日期：2006-12-01 00:00:00
abstract：:In order to characterize in vivo gene mutations that occur during fetal development, molecular analyses were undertaken of mutant 6-thioguanine resistant T-lymphocytes isolated from placental cord blood samples of 13 normal male newborns. These mutant T-cells were studied to define hypoxanthine-guanine phosphoribosylt...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.2850140404
更新日期：1989-01-01 00:00:00
abstract：:Exposure to inorganic arsenic increases the risk of basal cell carcinoma (BCC). Arsenic metabolism is a susceptibility factor for arsenic toxicity, and specific haplotypes in arsenic (+3 oxidation state) methyltransferase (AS3MT) have been associated with increased urinary fractions of the most toxic arsenic metabolit...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.21896
更新日期：2015-01-01 00:00:00
abstract：:Malignant gliomas are heterogeneous populations of dynamically interacting cells. Genomic and transcriptional changes define this cellular hierarchy and allow certain tumor cells to co-opt metabolic machinery and adopt gene expression profiles that promote cellular reprogramming. Resultant expansion of privileged subp...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/em.21988
更新日期：2016-06-01 00:00:00
abstract：:Oxidative damage (lipid peroxidation, LPO) induced in a completely defined system containing glutathione (GSH), purified gamma-glutamyl transpeptidase (GGT), and EDTA- and ADP-chelated ferric iron was enhanced by catalytic amounts of cupric ions and by ceruloplasmin (CP). The enhancement depended on GSH concentration,...
journal_title：Environmental and molecular mutagenesis
pub_type： 杂志文章
doi：10.1002/(sici)1098-2280(1997)29:1<73::aid-em10>3.0
更新日期：1997-01-01 00:00:00
