Abstract:
:The accessibility of reactive metabolites to test cells is critical for a genotoxic response. However, sulfo-conjugates formed outside may not readily enter cells, and some metabolites formed by cytochromes P450 (CYPs) may not endure transport. This topic was addressed in the present study, using V79 cells engineered for human CYPs and/or a sulfotransferase (SULT). First, 1-methylpyrene, 1-hydroxymethylpyrene, benzo[a]pyrene, and aflatoxin B1 significantly induced micronuclei in V79-hCYP1A2-hSULT1A1, V79-hSULT1A1, V79-hCYP1A1, and V79-hCYP1A2 cells, respectively. Subsequently, we used these cell lines as external activating systems in various experimental settings in combination with V79-derived target cells lacking critical enzymes. 1-Methylpyrene (activated by CYPs and SULTs sequentially) showed an activity similar to that in V79-hCYP1A2-hSULT1A1 cells, in each following model: a mixed V79-hCYP1A2:V79-hSULT1A1 (1:1) culture, exposure of V79-hCYP1A2 to 1-methylpyrene followed by transfer of medium to V79-hSULT1A1 target cells, and V79-hSULT1A1 communicating with V79-hCYP1A2 through 0.4-μm pores and over a 1-mm distance in a unique transwell system. These results suggest ready transfer of 1-hydroxymethylpyrene formed in V79-hCYP1A2 to V79-hSULT1A1 for further activation. In the last two models, with V79-hSULT1A1 for activation and V79-Mz as target, 1-hydroxymethylpyrene induced micronuclei mildly, suggesting limited intercellular transfer of the ultimate genotoxicant, 1-sulfooxymethylpyrene. Benzo[a]pyrene induced micronuclei in V79-Mz communicating with V79-hCYP1A1 via porous membranes, whereas aflatoxin B1 was inactive in V79-Mz communicating with V79-hCYP1A2. Our results suggest that the sulfo-conjugate tested may have difficulty entering cells for a genotoxic effect, and the reactive metabolite of aflatoxin B1, unlike that of benzo[a]pyrene, could not travel an adequate distance to enter cells. Environ. Mol. Mutagen. 61:224-234, 2020. © 2019 Wiley Periodicals, Inc.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Zhu N,Hu K,Li Z,Chen Y,Liu Ydoi
10.1002/em.22309subject
Has Abstractpub_date
2020-02-01 00:00:00pages
224-234issue
2eissn
0893-6692issn
1098-2280journal_volume
61pub_type
杂志文章abstract::A study of meiotic and postmeiotic germ-cell-stage sensitivity of male mice to induction of unscheduled DNA synthesis (UDS) by acrylamide showed that DNA repair could be detected in early spermatocytes (after the last scheduled DNA synthesis) through about mid-spermatid stages. No DNA repair could be detected in later...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850160302
更新日期:1990-01-01 00:00:00
abstract::Nitrous acid (NA) is often presumed to cause base substitutions in organisms with double-stranded DNA as a direct consequence of oxidative deamination of adenine and of cytosine residues. Here we summarize evidence indicating that other mechanisms are involved in the case of NA-induced G/C-->A/T transition mutations. ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850240305
更新日期:1994-01-01 00:00:00
abstract::Increased telomerase expression has been implicated in the pathogenesis of lung cancer and, since the primary cause of lung cancer is smoking, an association between telomerase reactivation and tobacco smoke has been proposed. In this work an investigation has been performed to assess the relationship between tobacco ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22127
更新日期:2017-10-01 00:00:00
abstract::The widespread application of carbon nanotubes (CNT) on industrial, biomedical, and consumer products can represent an emerging respiratory occupational hazard. Particularly, their similarity with the fiber-like shape of asbestos have raised a strong concern about their carcinogenic potential. Several in vitro and in ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.22177
更新日期:2018-05-01 00:00:00
abstract::In industrialized countries, heart disease rates are higher among women after menopause. Recent studies indicate that consumption of phytoestorogens, e.g., isoflavones such as genistein (GE), may have potential cardiovascular health benefits; however, no studies have evaluated the effect of these agents on toxicant-in...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20080
更新日期:2005-01-01 00:00:00
abstract::Three carbamate insecticides (propoxur, methomyl, and aldicarb) were evaluated for their ability to induce micronuclei (MN) in vitro using cultured Chinese hamster ovary (CHO) cells, and in vivo in mouse bone marrow erythrocytes. In vitro, all three insecticides induced a significant increase in micronucleated binucle...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::An automated approach for scoring in vitro micronuclei (MN) has been described in which flow cytometric analysis is combined with compound exposure, processing, and sampling in a single 96-well plate (Bryce SM et al. [2010]: Mutat Res 703:191-199). The current report describes protocol optimization and an interlaborat...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21760
更新日期:2013-04-01 00:00:00
abstract::The mechanism of toxicity of the leukemogen benzene is not entirely known. This pilot study used RNA-sequencing (RNA-seq) technology to examine the effect of benzene exposure on gene expression in peripheral blood mononuclear cells obtained from 10 workers occupationally exposed to high levels of benzene (≥5 ppm) in a...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21801
更新日期:2013-08-01 00:00:00
abstract::Two phenotypic classes of selectable tk-/- mutants have been isolated from the TK6 human lymphoblast cell line; one has a normal growth rate (tkn) relative to the parental cell line; the other has a slow growth rate (tks). Complete karyotypes of metaphase chromosomes were prepared and analyzed from 16 tks mutants (eig...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850140304
更新日期:1989-01-01 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::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::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::Lung cancer is the leading cause of cancer mortality in Taiwanese women. Cigarette smoking cannot explain the high lung cancer mortality in this population because less than 10% of women in Taiwan are smokers. Therefore, environmental factors other than smoking may play an important role in lung cancer development in ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.1037
更新日期:2001-01-01 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::Hypertension is often treated with diuretics, like hydrochlorothiazide (HCTZ). Previous results on the in vitro genotoxicity of HCTZ are equivocal. In the present study, we have evaluated the genotoxicity of HCTZ in cultured human lymphocytes using the Cytokinesis Blocked Micronucleus (CBMN) assay. In addition, micron...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20180
更新日期:2006-04-01 00:00:00
abstract::Experiments described herein were designed to evaluate the performance characteristics of a flow cytometry-based system that scores the incidence of peripheral blood micronucleated reticulocytes (MN-RETs). These procedures represent the continued refinement of a previously reported anti-CD71-based method (Dertinger et...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20075
更新日期:2004-01-01 00:00:00
abstract::Methyl 3,4-diphenyl-5-hydroxylamino-2-furoate (N-OH-MDPF) (I), methyl 3,4-diphenyl-5-acetoxyamino-2-furoate (N-OAc-MDPF) (II), methyl 3,4-diphenyl-N-hydroxy-5-acetylamino-2-furoate (N-OH-MDPAF) (III), and methyl 3,4-diphenyl-N-acetoxy-5-acetylamino-2-furoate (N-OAc-MDPAF) (IV) were synthesized and tested for mutagenic...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850170204
更新日期:1991-01-01 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::Human immunodeficiency virus (HIV)-infected pregnant women are administered nucleoside-analogue antiretrovirals to reduce maternal-infant viral transmission. The current protocol recommends treating newborns for 6 additional weeks postpartum. The treatment is effective, but the risk of drug-induced chromosomal damage ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10210
更新日期:2004-01-01 00:00:00
abstract::Coumarin (1,2-benzopyrone), a natural food constituent, prevents polycyclic aromatic hydrocarbon-induced neoplasms in rats and mice, but has not been studied with other chemical carcinogens. We examined coumarin chemoprotection against aflatoxin B1 using the 6-thioguanine resistance mutation assay in two different Chi...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2280(1998)32:1<64::aid-em8>3.0.
更新日期:1998-01-01 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::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::A rapid and simple procedure for the micronucleus test (MNT) in vitro using Chinese hamster ovary (CHO) cells was established in our laboratory. The assay is intended to quickly screen chromosomal aberrations in vitro within the framework of industrial genotoxicity studies. To test the sensitivity of the assay in the ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850260309
更新日期:1995-01-01 00:00:00
abstract::Several types of diesel exhaust particles (DEPs) have been used for toxicology studies, including a high-organic automobile DEP (A-DEP) from Japan, and a low-organic forklift DEP developed by the National Institute of Standards and Technology (N-DEP). However, these DEPs were not characterized extensively for chemical...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21812
更新日期:2013-12-01 00:00:00
abstract::This paper summarizes recent developments in the continuing evolution of Human Relevance Frameworks to systematically consider the weight of evidence of hypothesized modes of action in animals and their potential human relevance for both cancer and non-cancer effects. These frameworks have been developed in initiative...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.20369
更新日期:2008-03-01 00:00:00
abstract::During the development of cancer a series of specific genetic alterations have to occur in a stepwise fashion to transform a normal somatic cell into a malignant tumor cell. These genetic changes can be roughly divided in two groups: mutations in proto-oncogenes that result in a constantly activated gene product and m...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 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 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::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::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