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 in the three assays currently recommended by the International Conference on Harmonization (ICH): bacterial mutagenesis in Salmonella typhimurium and Escherichia coli, mammalian cell mutagenesis in L5178Y mouse lymphoma cells, and micronucleus induction in rat bone marrow. A small but statistically significant increase in revertant colonies was produced by CQ with Salmonella tester strain TA98 without metabolic activation (MA) and by AQ-13 with strain TA1537 both with and without MA. In L5178Y cells, testing of CQ and AQ-13 up to cytotoxic concentrations with and without MA produced no increase in mutant colonies and no increase in the numbers of small colonies. Slight decreases in the ratio of polychromatic erythrocytes (PCE) to red blood cells (RBC) were observed in male and female rats treated with CQ and in females only treated with AQ-13; however, none of these changes was statistically significant. No increases in the frequency of micronucleated PCE were observed at any dose level of CQ or AQ-13. Although both CQ and AQ-13 showed weak bacterial mutagenicity, this mutagenic effect was not confirmed in either the mouse lymphoma mutagenesis assay or the micronucleus assay. These results indicate that CQ and AQ-13 should pose minimal risk of genotoxic damage in human populations being administered these drugs.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Riccio ES,Lee PS,Winegar RA,Krogstad DJ,De D,Mirsalis JCdoi
10.1002/em.1052subject
Has Abstractpub_date
2001-01-01 00:00:00pages
69-79issue
1eissn
0893-6692issn
1098-2280pii
10.1002/em.1052journal_volume
38pub_type
杂志文章abstract::Occupational exposure to pesticides in tobacco fields causes genetic damage in farmers. The aim of this study was to analyze tobacco farmers chronically exposed to low doses of pesticides and nicotine (present in the tobacco leaves) in relation to absolute telomere length (aTL), and explore the influence of lifestyle ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21984
更新日期:2016-01-01 00:00:00
abstract::As a contribution to the second round of rodent carcinogenesis prediction organised by the U.S. National Institute of Environmental Health Sciences (NIEHS), speculative predictions for 30 chemicals currently under evaluation in U.S. National Toxicology Program (NTP) rodent bioassays are presented. Core chemical data r...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)27:3<237::AID-EM9>3.0
更新日期:1996-01-01 00:00:00
abstract::Riddelliine (RID) is a pyrrolizidine alkaloid found in plants of the genera Crotalaria, Amsinckia, and Senecio in the United States. RID has been extensively studied in a wide variety of in vitro short-term genotoxicity tests and has yielded positive responses in most test systems; however, there are fewer data availa...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850210310
更新日期:1993-01-01 00:00:00
abstract::Third instar larvae of Drosophila melanogaster transdihybrid for mwh and flr were exposed to varying concentrations of cisplatin by feeding on dry media wetted with aqueous solutions of the test compound. Larval feeding continued until pupation, and surviving transdihybrid adults were collected seven days following co...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850100210
更新日期:1987-01-01 00:00:00
abstract::DNA damage induced by solar ultraviolet (UV) radiation plays an important role in the induction of skin cancer. Although UVA constitutes the majority of solar UV radiation, it is less damaging to DNA than UVB. The DNA damage produced by UVA radiation, however, can be augmented in the presence of a photosensitizer. We ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20166
更新日期:2006-01-01 00:00:00
abstract::Coal tar (CT) is a thick black liquid produced as a by-product of coal carbonization to produce coke or manufactured gas. It is comprised a complex mixture of polycyclic aromatic compounds, including a wide range of polycyclic aromatic hydrocarbons (PAHs), many of which are genotoxic and carcinogenic. CT is used in so...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22032
更新日期:2016-08-01 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::Atmospheric pollution represents a relevant environmental hazard which has been associated with considerable excess mortality, morbidity, and increased rates of respiratory diseases in humans. To date, more than 3,000 environmental chemical compounds have been identified in the ambient atmosphere, including a variety ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
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::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::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:BACKGROUND:Recently, high concentrations of arsenic have been documented in ground waters of Southern Assam, India. Indiscriminate smokeless tobacco consumption is a common practice in this region. Correlation between nutritional status and arsenic and smokeless tobacco-induced health effects has not been taken up in h...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22188
更新日期:2018-06-01 00:00:00
abstract::We have used an SV40-based shuttle vector, pZ189, to investigate the capacity of HeLa cell extracts to reproduce the in vivo process of mutation fixation. We showed previously that when UV-irradiated pZ189 is replicated in these extracts, bypass of UV photoproducts occurs, resulting in base substitution mutations in t...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850260207
更新日期:1995-01-01 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::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::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::Therapy-related leukemia has been a recognized sequela of cancer treatment for decades with "signature" abnormalities of chromosomes 5, 7, and 11 observed in treated patients. Risk to oncology personnel handling anti-cancer agents has also been documented by non-specific measures of genotoxicity in blood and urine. Us...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21852
更新日期:2014-05-01 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::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::Paraoxon (diethyl-p-nitrophenylphosphate) is the toxic, but non-mutagenic metabolite of the organophosphorus ester (OP) insecticide parathion. Although this agent has been used as a deacetylase inhibitor in many studies, we discovered a mutagenic synergy with paraoxon and plant-activated m-phenylenediamine or with dir...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Tandem-base mutations (TBM) are associated with ultraviolet light and other mutagens. Herein, we report an age- and tissue-specific difference in the frequency of spontaneous TBM in Big Blue transgenic mice. A total of 390 mutants from liver and adipose tissue contained 17 and 4 TBM, respectively, while no TBM were de...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2280(1999)33:4<320::aid-em9>3.0
更新日期:1999-01-01 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::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::Peripheral lymphocytes from Taiwanese women (n = 35) exposed to polychlorinated aromatic hydrocarbons and from matched controls (n = 24) were assessed for the levels of sister chromatid exchanges (SCEs) after a 72-hour incubation of whole blood in the presence or absence of alpha-naphthoflavone (ANF) and for chromosom...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850110103
更新日期:1988-01-01 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::The mutational spectrum for 28 X-ray induced mutations and 2 spontaneous mutations, previously determined by genetic and cytogenetic methods, consisted of 20 multilocus deficiencies (19 induced and 1 spontaneous) and 10 intragenic mutations (9 induced and 1 spontaneous). One of the X-ray induced intragenic mutations w...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850180303
更新日期:1991-01-01 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 aim of this research was to study the gaseous and particulate emissions of genotoxic substances during cooking with two types of methane stoves (a new one and an old one). The particulates were sampled both with a cascade impactor air sampler and an impinger with ice trap and analyzed by two bacterial mutagenicity...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 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::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