Abstract:
:There is scientific and regulatory interest in using mutation assays in transgenic mice in safety assessments for new chemicals and drugs. Currently these assays are in the process of being validated, and protocols for routine testing are being defined. Some of the issues and results to date with regard to assay validation include reproducibility of the assay results (they are qualitatively reproducible), relevance of the test system (the transgene closely approximates an endogenous mammalian gene as a mutational target for the limited number of compounds tested), and the predictivity of the assay for heritable effects (unknown at this time) or carcinogenicity (the assays show good positive predictivity for carcinogenicity; the negative predictivity of the assay requires further investigation). Definition of appropriate study protocols for routine testing requires that applicable statistical methods are available and that the experimental parameters that affect the detection of mutations are known. Progress made in identifying these parameters is discussed. A proposal is made for the custom design of routine safety studies, which is based on the anticipated use of each individual test agent. A working group has been formed to conduct some of the studies still required for validation of these assays.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Gorelick NJdoi
10.1002/em.2850250309subject
Has Abstractpub_date
1995-01-01 00:00:00pages
218-30issue
3eissn
0893-6692issn
1098-2280journal_volume
25pub_type
杂志文章,评审abstract::Clustered damage induced by ionizing radiation--two or more oxidized bases, abasic sites, or strand breaks within a few DNA helical turns--have been postulated to be major lethal and/or mutagenic sites. Although they have recently been shown to be induced in genomic DNAs by ionizing photons and particles, little is kn...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.1067
更新日期:2001-01-01 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::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::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::Environmental tobacco smoke (ETS) is a major source of indoor air pollution. Extractable-respirable particulate (ERP) from the ETS-contaminated indoor air (ERP-ETS) was collected from six passenger train cars and one control room. The mutagenicity of ERP-ETS was tested in the Ames/Salmonella test in the presence of ma...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2280(1999)33:3<185::aid-em2>3.0
更新日期:1999-01-01 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::Non-isotopic in situ hybridization using a mouse gamma (major) satellite probe DNA was applied to detect centromeres in micronuclei, which were induced in vitro in mouse liver cells by ionizing radiation and by vinblastine sulfate. In a cytokinesis-blocked micronucleus assay a dose-dependent induction of micronuclei w...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850190102
更新日期:1992-01-01 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 interstrand crosslinks (ICLs) are covalent linkages between two strands of DNA, and their presence interferes with essential metabolic processes such as transcription and replication. These lesions are extremely toxic, and their repair is essential for genome stability and cell survival. In this review, we will di...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.21736
更新日期:2012-12-01 00:00:00
abstract::Genotoxic effects of therapeutic ultrasound are poorly documented, when compared with the wide use of this physical agent. The aim of this work was to investigate the clastogenic and aneugenic potential of 1 MHz ultrasound, employing intensities (200 and 300 mW/cm2 ) above the cavitational threshold, but in the range ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22124
更新日期:2018-01-01 00:00:00
abstract::Genomes of all living organisms are constantly threatened by endogenous and exogenous agents that challenge the chemical integrity of DNA. Most bacteria have evolved a coordinated response to DNA damage. In Escherichia coli, this inducible system is termed the SOS response. The SOS global regulatory network consists o...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.22267
更新日期:2019-05-01 00:00:00
abstract::Aldehydes are widespread environmental and industrial compounds, able to stimulate a range of adverse health effects (e.g., general toxicity, allergenic reactions, mutagenicity, and carcinogenicity). We have previously presented quantitative structure-activity relationships (QSARs) for the genotoxicity of simple and a...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20158
更新日期:2005-12-01 00:00:00
abstract::Gravid Swiss Webster dams were injected via tail vein with a single (1.1, 2.2, or 3.3 mmol/kg) dose of ethyl carbamate (urethane) on days 13-17 of pregnancy. Relative sister chromatid exchange (SCE) responses in maternal bone marrow vs. individual fetal liver cells were assessed. In addition, in order to evaluate the ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850140204
更新日期:1989-01-01 00:00:00
abstract::Quinoline is a specific and potent carcinogen to the rat and mouse liver. Studies are described here in which it was evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the rat liver in vivo. Although some individual animals showed indications of a marginal response the absence of clear group posi...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850140403
更新日期:1989-01-01 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::Studies of the mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L. (Bignoniaceae), were performed using the liquid preincubation method of the Salmonella/microsome test. At the highest dose tested, 100 micrograms/plate, both compounds showed no mutagenicity and ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850200409
更新日期:1992-01-01 00:00:00
abstract::We evaluated the effects of urban air pollutants on human nasal mucosa over an 8-month period on 102 subjects living in Florence, Tuscany, Italy. A group of subjects living in a city with a lower level of pollution (Sassari, Sardinia, Italy) was also analyzed. Nasal mucosa cells were harvested by brushing, a noninvasi...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10188
更新日期:2003-01-01 00:00:00
abstract::Occupational exposure to coal dust causes coal workers' pneumoconiosis (CWP), which is a chronic inflammatory and fibrotic lung disease. Recently, chronic inflammation has been accepted as a crucial factor in the pathogenesis of neoplasia. The chronic inflammation provides dynamic setting for oxidative stress and form...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20377
更新日期:2008-04-01 00:00:00
abstract::Previously, we determined that elimination of deoxycytidylate (dCMP) deaminase (DCD1) in the yeast Saccharomyces cerevisiae increases the intracellular dCTP:dTTP ratio and reduces the induction of G x C --> A x T transitions in the SUP4-o gene by ethyl methanesulfonate (EMS) and N-methyl-N'-nitro-N-nitrosoguanidine (M...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Gene therapy has been proposed to have implications in the treatment of cancer. By genetically manipulating the hematopoietic stem cell compartment with genes that confer resistance to chemotherapeutic agents, the dose escalation that is necessary to effectively treat the cancers could potentially be achieved. DNA rep...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/(sici)1098-2280(2000)35:2<71::aid-em1>3.0.
更新日期:2000-01-01 00:00:00
abstract::N-Hydroxymethylacrylamide (NHMA), a mouse carcinogen inactive in the Salmonella assay and mouse micronucleus (MN) assay, was tested for reproductive effects in a mouse continuous breeding study. In that study, increased embryonic deaths were observed after 13 weeks exposure of parental animals to NHMA via drinking wat...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10139
更新日期:2003-01-01 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::Arsenic is a world health problem due to the seriousness of its effects, mainly related with the increase of cancer. In Chile, the geological characteristics of the northern region, associated with the development of the copper mining and smelting activities, have contributed to increase the environmental levels of ar...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20374
更新日期:2008-04-01 00:00:00
abstract::Big Blue Rat-2 cells were evaluated for mutagenesis and mutational spectra (spontaneous and ethylnitrosourea [ENU]-induced). Survival, mutant frequency, population doubling time, and kinetics of mutant increase (to 120 hr) were determined. Exposures were 100, 200, 400, 600, and 1,000 micrograms ENU/ml. The spontaneous...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)28:4<325::AID-EM5>3.0
更新日期:1996-01-01 00:00:00
abstract::In this study we compared the ability of extractable organic material from particulate and semivolatile fractions of gasoline emission to induce mutations in bacteria and form adducts with calf thymus (CT) DNA with corresponding data obtained from diesel exhaust. Exhaust particles from gasoline-powered passenger cars ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10172
更新日期:2003-01-01 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 influence of several methodological factors on mean values of sister chromatid exchanges (SCEs) and micronuclei (MN) in peripheral lymphocytes of 1,650 subjects was analyzed. Donors belonged to a general healthy population living in Pisa and in two nearby small cities: Cascina and Navacchio (Ca-Na). Blood samples ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2280(1998)31:3<218::aid-em3>3.0
更新日期:1998-01-01 00:00:00
abstract::A wild-type strain of herpes simplex virus type 1 (HSV-1:KOS) encoding a functional thymidine kinase (tk+) and a tk- mutant strain (HSV-1:PTK3B) were used to study the role of the viral tk in the repair of UV-irradiated HSV-1 in human cells. UV survival of HSV-1:PTK3B was substantially reduced compared with that of HS...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850150104
更新日期:1990-01-01 00:00:00
abstract::Coal is the largest fossil fuel source used for the generation of energy. However, coal extraction and its use constitute important pollution factors; thus, risk characterization and estimation are extremely important for the safety of coal workers and the environment. Candiota is located to the southeast of the state...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21744
更新日期:2013-01-01 00:00:00
abstract::Halogenated acetonitriles (HANs) are known to be water disinfectant by-products. Their mutagenicity and carcinogenicity have been shown in different test systems in vivo and in vitro. They also have clastogenic properties. In this study, the ability of HAN to induce single-strand breaks on the DNA of HeLa S3 cells was...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/1098-2280(2000)36:1<52::aid-em8>3.0.co;2-9
更新日期:2000-01-01 00:00:00