Chromosomal effects of non-alkylating drug exposure in oncology personnel.

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. Using chromosomal markers applied in clinical practice, we previously demonstrated in oncology workers, a dose-related increase in abnormalities of chromosomes 5 and 7, known to be targets of alkylating agent exposure. In the analysis presented here, we extended that work to also assess damage resulting from non-alkylating drug exposure. Peripheral blood lymphocytes from oncology personnel (N = 63) and non-exposed controls (N = 46) was collected and examined using the fluorescent in situ hybridization technique with probes for targets on chromosomes 5, 7, and 11. Participants recorded drug handling events over a 6 week period. Important co-variates were considered. Examining chromosomal outcomes as a function of drug handling frequency, we employed Poisson Regression to obtain incident rate ratios (IRRs) for selected drug handling frequencies. We found a dose-related increase in the IRR for aberrations in all three chromosomes 5, 7, and 11, reaching statistical significance for chromosome 5, as a function of non-alkylating drug handling. This suggests that the targeting of chromosome 5 is not limited to alkylating agent exposure, as some recent evidence in treated patients has also shown. Thus, the pattern of insult observed in treated patients appears to extend to oncology personnel exposed in the workplace.

journal_name

Environ Mol Mutagen

authors

McDiarmid MA,Rogers B,Oliver MS

doi

10.1002/em.21852

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

369-74

issue

4

eissn

0893-6692

issn

1098-2280

journal_volume

55

pub_type

杂志文章
  • Genotoxicological investigation of hospital nurses occupationally exposed to ethylene-oxide: I. Chromosome aberrations, sister-chromatid exchanges, cell cycle kinetics, and UV-induced DNA synthesis in peripheral blood lymphocytes.

    abstract::Structural, and numeric chromosome aberrations (CA), sister-chromatid exchange (SCE), phytohemagglutinin stimulation (LI), proliferative rate index (PRI), and UV light-induced unscheduled DNA-synthesis (UDS) were investigated in peripheral blood lymphocytes (PBL) of 48 historical controls ("Controls"); of 14 hospital ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2280(1996)27:2<84::AID-EM2>3.0.

    authors: Major J,Jakab MG,Tompa A

    更新日期:1996-01-01 00:00:00

  • Persistence of micronuclei in peripheral blood normochromatic erythrocytes of subchronically benzene-treated male mice.

    abstract::The kinetics of micronucleus (MN) induction and decline in blood normochromatic erythrocytes (NCE) of mice subchronically exposed to benzene was investigated during and after exposure. Swiss (ICR) male mice (10/group) were given 0.0, 36.6, 73.2, and 146.4 mg/kg body weight benzene by gavage daily for 14 days, except f...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2860120306

    authors: Rithidech K,Au WW,Ramanujam VM,Whorton EB Jr,Legator MS

    更新日期:1988-01-01 00:00:00

  • Heterozygous Aprt mouse model: detection and study of a broad range of autosomal somatic mutations in vivo.

    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:

    authors: Vrieling H,Wijnhoven S,van Sloun P,Kool H,Giphart-Gassler M,van Zeeland A

    更新日期:1999-01-01 00:00:00

  • Does increase in DNA repair allow "tolerance-to-insult" in chemical carcinogenesis? Skin tumor experiments with MGMT-overexpressing mice.

    abstract::Several genotoxicity endpoints have been evaluated to define nonlinear dose-responses for SN 1 and SN 2 alkylating genotoxicants. Dose-response studies acknowledging the process of multistage tumorigenesis are important; however, data pertaining nonlinearity are not yet available. In this communication, the role of DN...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21834

    authors: Becker K,Thomas AD,Kaina B

    更新日期:2014-03-01 00:00:00

  • Analysis of mutations induced by replication of UV-damaged plasmid DNA in HeLa cell extracts.

    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

    authors: Carty MP,el-Saleh S,Zernik-Kobak M,Dixon K

    更新日期:1995-01-01 00:00:00

  • Spontaneous mutation of the lacI transgene in rodents: absence of species, strain, and insertion-site influence.

    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

    authors: Zhang S,Glickman BW,de Boer JG

    更新日期:2001-01-01 00:00:00

  • Global gene expression response of a population exposed to benzene: a pilot study exploring the use of RNA-sequencing technology.

    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

    authors: Thomas R,McHale CM,Lan Q,Hubbard AE,Zhang L,Vermeulen R,Li G,Rappaport SM,Yin S,Rothman N,Smith MT

    更新日期:2013-08-01 00:00:00

  • Sources of variability in data from a lacI transgenic mouse mutation assay.

    abstract::Experimental features of a transgenic mouse mutation assay based on a lacI target transgene from Escherichia coli are considered in detail. Sources of variability in the experimental protocol that can affect the statistical nature of the observations are examined with the goal of identifying sources of excess variatio...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850230105

    authors: Piegorsch WW,Lockhart AM,Margolin BH,Tindall KR,Gorelick NJ,Short JM,Carr GJ,Thompson ED,Shelby MD

    更新日期:1994-01-01 00:00:00

  • Mutational spectra in transgenic animal research: data analysis and study design based upon the mutant or mutation frequency.

    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.

    authors: Carr GJ,Gorelick NJ

    更新日期:1996-01-01 00:00:00

  • Mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L.

    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

    authors: Chulasiri M,Bunyapraphatsara N,Moongkarndi P

    更新日期:1992-01-01 00:00:00

  • Early years of the Salmonella mutagen tester strains: lessons from hycanthone.

    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

    authors: Hartman PE

    更新日期:1989-01-01 00:00:00

  • Reproductive integrity of mammalian cells exposed to power frequency electromagnetic fields.

    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

    authors: Livingston GK,Witt KL,Gandhi OP,Chatterjee I,Roti Roti JL

    更新日期:1991-01-01 00:00:00

  • Differential sensitivity of mouse oocytes to colchicine-induced aneuploidy.

    abstract::Unpublished results from our laboratory showed that colchicine increased the incidence of hyperploid mouse metaphase II (MII) oocytes when injected at the same time as human chorionic gonadotrophin (HCG). The objective of the present study was to determine whether the time of administering colchicine influenced the in...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850100208

    authors: Mailhes JB,Yuan ZP

    更新日期:1987-01-01 00:00:00

  • Comparative overview of current international strategies and guidelines for genetic toxicology testing for regulatory purposes.

    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 t...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.20216

    authors: Cimino MC

    更新日期:2006-06-01 00:00:00

  • Three-color labeling method for flow cytometric measurement of cytogenetic damage in rodent and human blood.

    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

    authors: Dertinger SD,Camphausen K,Macgregor JT,Bishop ME,Torous DK,Avlasevich S,Cairns S,Tometsko CR,Menard C,Muanza T,Chen Y,Miller RK,Cederbrant K,Sandelin K,Pontén I,Bolcsfoldi G

    更新日期:2004-01-01 00:00:00

  • Protective effects of a mixture of antioxidant vitamins and minerals on the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster.

    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

    authors: Costa WF,Nepomuceno JC

    更新日期:2006-01-01 00:00:00

  • Hypermethylation of CpG islands is associated with increasing chromosomal damage in chinese lead-exposed workers.

    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

    authors: Yu LB,Tu YT,Huang JW,Zhang YN,Zheng GQ,Xu XW,Wang JW,Xiao JQ,Christiani DC,Xia ZL

    更新日期:2018-07-01 00:00:00

  • Molecular analyses of in vivo hprt mutations in human T-lymphocytes: IV. Studies in newborns.

    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

    authors: McGinniss MJ,Nicklas JA,Albertini RJ

    更新日期:1989-01-01 00:00:00

  • Specific numerical chromosomal aberrations induced by adriamycin.

    abstract::Fluorescence in situ hybridization with 7, 17, X, and Y chromosome-specific DNA probe was used to investigate the ability of Adriamycin (AM) to induce aneuploidy in interphase human lymphocytes. The reliability of the probes was tested by hybridization to metaphases and interphase nuclei of untreated normal lymphocyte...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2280(1999)33:2<161::aid-em8>3.0

    authors: Aly MS,Othman OE,El Nahas SM

    更新日期:1999-01-01 00:00:00

  • A functional SNP in the 3'-UTR of TAP2 gene interacts with microRNA hsa-miR-1270 to suppress the gene expression.

    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

    authors: Knox B,Wang Y,Rogers LJ,Xuan J,Yu D,Guan H,Chen J,Shi T,Ning B,Kadlubar SA

    更新日期:2018-03-01 00:00:00

  • The influence of DNA repair by Ogt alkyltransferase on the distribution of alkylnitrosourea-induced mutations in Escherichia coli.

    abstract::To determine the influence of DNA repair by Ogt alkyltransferase on the distribution of alkylnitrosourea-induced mutations, we have analysed in Ogt-proficient and Ogt-deficient bacterial strains the DNA sequence changes of a total of 357 independent mutations occurring within the initial part of the lacl gene of Esche...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2280(1997)29:2<180::aid-em9>3.0

    authors: Vidal A,Abril N,Pueyo C

    更新日期:1997-01-01 00:00:00

  • Induction of genetic recombination: consequences and model systems.

    abstract::Radiation and many chemicals have been found to induce homologous genetic recombination. Experimental systems that allow the detection and characterization of recombinagens exist in organisms as diverse as bacteria, fungi, plants, insects, and mammals. Recombination plays an important role in many biological processes...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.2850230614

    authors: Hoffmann GR

    更新日期:1994-01-01 00:00:00

  • Micronucleus assay for mouse alveolar Type II and Clara cells.

    abstract::The objective of our study was to develop a micronucleus (MN) assay for detecting genotoxic damage after inhalation exposure in mouse alveolar Type II and Clara cells, potential target cells for lung carcinogens. Ten male C57BL/6J mice were exposed to ethylene oxide (630 mg/m(3)) for 4 hr via inhalation; 10 unexposed ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20520

    authors: Lindberg HK,Falck GC,Catalán J,Santonen T,Norppa H

    更新日期:2010-03-01 00:00:00

  • Evaluation of the potential of riddelliine to induce unscheduled DNA synthesis, S-phase synthesis, or micronuclei following in vivo treatment with multiple doses.

    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

    authors: Mirsalis JC,Steinmetz KL,Blazak WF,Spalding JW

    更新日期:1993-01-01 00:00:00

  • Genetic toxicology and toxicogenomic analysis of three cigarette smoke condensates in vitro reveals few differences among full-flavor, blonde, and light products.

    abstract::Cigarette smoking leads to various detrimental health outcomes. Tobacco companies produce different brands of cigarettes that are marketed as reduced harm tobacco products. Early examples included "light" cigarettes, which differ from regular cigarettes due to filter ventilation and/or differences in chemical constitu...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21689

    authors: Yauk CL,Williams A,Buick JK,Chen G,Maertens RM,Halappanavar S,White PA

    更新日期:2012-05-01 00:00:00

  • Tissue-specific and time-dependent clonal expansion of ENU-induced mutant cells in gpt delta mice.

    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

    authors: Nakayama T,Sawai T,Masuda I,Kaneko S,Yamauchi K,Blyth BJ,Shimada Y,Tachibana A,Kakinuma S

    更新日期:2017-10-01 00:00:00

  • Centromere detection in vinblastine- and radiation-induced micronuclei of cytokinesis-blocked mouse cells by using in situ hybridization with a mouse gamma (major) satellite DNA probe.

    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

    authors: Salassidis K,Huber R,Zitzelsberger H,Bauchinger M

    更新日期:1992-01-01 00:00:00

  • Cytogenetic biomonitoring in traffic police workers: micronucleus test in peripheral blood lymphocytes.

    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:

    authors: Bolognesi C,Merlo F,Rabboni R,Valerio F,Abbondandolo A

    更新日期:1997-01-01 00:00:00

  • Mechanism of induction of chromosomal aberrations by inhibitors of DNA topoisomerases.

    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

    authors: Palitti F

    更新日期:1993-01-01 00:00:00

  • Pyruvate remediation of cell stress and genotoxicity induced by haloacetic acid drinking water disinfection by-products.

    abstract::Monohaloacetic acids (monoHAAs) are a major class of drinking water disinfection by-products (DBPs) and are cytotoxic, genotoxic, mutagenic, and teratogenic. We propose a model of toxic action based on monoHAA-mediated inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a target cytosolic enzyme. This mo...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21795

    authors: Dad A,Jeong CH,Pals JA,Wagner ED,Plewa MJ

    更新日期:2013-10-01 00:00:00