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 repair genes are some of the potential candidates to confer increased resistance to chemotherapeutic agents. Although initial focus in this area has been on the direct reversal protein (MGMT), its protective ability is limited to those agents that produce O(6)-methylGuanine cross-links-agents that are not extensively used clinically (e.g., nitrosoureas). Furthermore, most alkylating agents attack more sites in DNA other than O(6)-methylGuanine, such that the protections afforded by MGMT may prevent the initial cytotoxicity, but at a price of increased mutational burden and potential secondary leukemias. Therefore, some of the genes that are being tested as candidates for gene transfer are base excision repair (BER) genes. We and others have found that overexpression of selective BER genes confers resistance to chemotherapeutic agents such as thiotepa, ionizing radiation, bleomycin, and other agents. As these "proof of concept" analyses mature, many more clinically relevant chemotherapeutic agents can be tested for BER protective ability.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Limp-Foster M,Kelley MRdoi
10.1002/(sici)1098-2280(2000)35:2<71::aid-em1>3.0.subject
Has Abstractpub_date
2000-01-01 00:00:00pages
71-81issue
2eissn
0893-6692issn
1098-2280pii
10.1002/(SICI)1098-2280(2000)35:2<71::AID-EM1>3.0.journal_volume
35pub_type
杂志文章,评审abstract::The in vivo Pig-a mutation assay has been adapted for measuring mutation in rats, mice, monkeys, and humans. To date, the assay has been used mainly to assess the mutagenicity of chemicals that are known to be powerful point mutagens. The assay has not been used to measure the biological effects associated with ionizi...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21724
更新日期:2012-10-01 00:00:00
abstract::Respirable crystalline silica has been classified as a human lung carcinogen. Ultrafine (diameter < 100 nm) silica particles may be important in carcinogenesis, although the mechanisms remain unclear. In the present study, WIL2-NS cells were incubated for 6, 24, and 48 hr with 0, 30, 60, and 120 microg/ml ultrafine cr...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20287
更新日期:2007-03-01 00:00:00
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
更新日期:1989-01-01 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::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::Mitochondria are dynamic organelles that are involved in a number of diverse processes. Most often the mitochondrion is associated with energy generation, but other important processes occur in this organelle such as fatty acid synthesis and amino acid metabolism. Although mitochondria encode less than 40 genes, all o...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20508
更新日期:2009-10-01 00:00:00
abstract::Experiments are described which elucidate some of the technical problems associated with the direct sequencing of polymerase chain reaction (PCR) amplified DNA. Sequencing primer purity, labeling methodology, and template preparation were explored. Conditions are presented for the routine sequencing of single- and dou...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850180413
更新日期:1991-01-01 00:00:00
abstract::Umu test is one of the in vitro genotoxicity test that has been used widely. It was developed as a high-throughput test system using the 96-well microplate. We have previously constructed new umu test strains for the evaluation of genotoxicity of procarcinogenic metabolic products formed by cytochrome P450 (CYP) enzym...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22092
更新日期:2017-05-01 00:00:00
abstract::The modulating effects of tannic acid (TA) on somatic mutation and mitotic recombination induced by methylmethanesulfonate (MMS), nitrogen mustard (HN2), and mitomycin C (MMC) were evaluated in the standard (ST) cross of the wing spot test in Drosophila melanogaster using co- and posttreatment protocols. It was shown ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/1098-2280(2000)36:3<195::aid-em2>3.0.co;2-
更新日期:2000-01-01 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::The effects of ultrasound on the cytoskeleton, comprising microtubules, had been studied decades ago. Nonetheless, very little attention has been paid to the effects of ultrasound on the mitotic spindle, which is also formed by microtubules. In this study, we treated human fibroblasts and human cancer cells (HeLa and ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22287
更新日期:2019-08-01 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::The placenta is a readily available source of material for molecular epidemiological investigations. As such, DNA damage in this tissue can be indicative of maternal exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs). Previous reports have demonstrated that (32)P-postlabeling (PPL) is...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/1098-2280(2000)36:4<274::aid-em3>3.0.co;2-
更新日期:2000-01-01 00:00:00
abstract::Micronuclei were assessed among the bone marrow PCEs of mice 28 hr after exposures to 1 to 8 Gy of X-rays and at 6-hr intervals from 12-60 hr after exposures to 2 or 6 Gy. At 28 hr, the frequency of micronuclei declined as the exposure level increased from 1 to 8 Gy. The peak proportion of micronucleated PCEs appeared...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850230209
更新日期:1994-01-01 00:00:00
abstract::The aim of this study was to investigate genotoxic effects of lamivudine (an analogue of cytidine) using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus (MN) tests in human peripheral lymphocytes. The cells were treated with 75, 100, 125, and 150 microg/ml concentrations of lamiv...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20393
更新日期:2008-05-01 00:00:00
abstract::Mentha piperita or peppermint is currently used for alleviating nausea, flatulence, and vomiting. In the present investigation, we evaluated the chemopreventive, antigenotoxic, and antioxidative effects of an aqueous extract of Mentha piperita leaves. One-day-old Swiss albino mice were treated with a single subcutaneo...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,收录出版
doi:10.1002/em.20185
更新日期:2006-04-01 00:00:00
abstract::The mitochondrial genome is essential for producing ATP (adenosine 5'-triphosphate) via oxidative phosphorylation. The gradual decline of mitochondrial function with age has long been postulated as a factor in aging. More recently, a variety of diseases have been related to molecular defects in human mitochondrial DNA...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.2850250607
更新日期:1995-01-01 00:00:00
abstract::Under the exposome paradigm all nongenetic factors contributing to disease are considered to be 'environmental' including chemicals, drugs, infectious agents, and psychosocial stress. We can consider these collectively as environmental stressors. Exposomics is the comprehensive analysis of exposure to all environmenta...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21985
更新日期:2015-12-01 00:00:00
abstract::DNA damage and its subsequent repair occur heterogeneously throughout the genome, which reflects the nature of the damaging agents, gross chromosomal structure, the specific nucleotide sequence, and transcriptional status. We selected to investigate the repair of DNA damage in an artificial, transgenic situation. Here...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 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 recent study conducted by our group showed that the NAT2 fast acetylator genotype is associated with an increasing risk for the development of colorectal cancer (CRC), especially for females. We therefore examined whether a higher risk of CRC in females with the NAT2 fast acetylator genotype was associated with the ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20444
更新日期:2009-03-01 00:00:00
abstract::The phenoxyherbicide and peroxisome proliferator 2-methyl-4-chlorophenoxyacetic acid (MCPA) was tested for its ability to induce sister-chromatid exchanges (SCE) in chick embryos. Erbitox E30 (a commercial formulation containing 28% MCPA sodium potassium salt as active ingredient) was injected into the air chamber in ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850190411
更新日期:1992-01-01 00:00:00
abstract::A cross-sectional study was designed to determine whether occupational exposure to a complex mixture of pesticides results in a significant increase of DNA damage in farmers chronically exposed to pesticides in open fields. Leukocytes from 47 agriculture workers exposed to pesticides and 50 controls were evaluated wit...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20435
更新日期:2009-01-01 00:00:00
abstract::A transplacental carcinogenicity study was conducted by exposing pregnant Swiss (CD-1) mice to 0, 50, 100, 200, or 300 mg 3'-azido-3'-deoxythymidine (AZT)/kg body weight (BW) daily for the duration of gestation (18-19 days) [National Toxicology Program,2006]. The incidence of alveolar/bronchiolar adenomas and carcinom...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20420
更新日期:2008-12-01 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::Tryptophan is metabolized through serotonin, indole, and kynurenine (KN) pathways. Uptake of an excess amount of tryptophan accompanied with vitamin B6 deficiency may result in the accumulation of higher concentrations of metabolites mainly from the KN pathways in the bladder. These metabolites could interact with nit...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.20588
更新日期:2011-03-01 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 cytotoxicity and mutagenicity of the human carcinogen, treosulphan, and its hydrolysis product, dl-1,2:3,4-diepoxybutane (DEB), were studied in Chinese hamster ovary, AS52, cells. Treosulphan (0.1-1.0 mM) is toxic and mutagenic at the gpt locus. A strong pH dependence was noted. DEB is cytotoxic and mutagenic at a...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850210113
更新日期:1993-01-01 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::Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. Although exposure to environmental agents appears to predispose individuals to this disease, little attention has been paid to the role of genetic susceptibility to environmental exposures in the etiology of childhood ALL. The enzymes GSTM...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20003
更新日期:2004-01-01 00:00:00