Identification of genes responsive to BPDE treatment in HeLa cells using cDNA expression assays

Yu, Zhe; Ford, Barry N.; Glickman, Barry W.

doi:10.1002/1098-2280(2000)36:3<201::aid-em3>3.0.co;2-1

Cited by 20 publications

(14 citation statements)

References 41 publications

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“…There was no great response in nucleotide excision repair genes on the microarrays in response to BaP and this is consistent with other microarray studies that have looked at the effects of BaP or its metabolites [ 3 , 8 , 10 ]. This is likely to be due to low constitutive expression of these important defence genes.…”

Section: Discussionsupporting

confidence: 89%

Time- and concentration-dependent changes in gene expression induced by benzo(a)pyrene in two human cell lines, MCF-7 and HepG2

et al. 2006

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Background: The multi-step process of carcinogenesis can be more fully understood by characterizing gene expression changes induced in cells by carcinogens. In this study, expression microarrays were used to monitor the activity of 18,224 cDNA clones in MCF-7 and HepG2 cells exposed to the carcinogen benzo(a)pyrene (BaP) or its non-carcinogenic isomer benzo(e)pyrene (BeP). Time and concentration gene expression effects of BaP exposure have been assessed and linked to other measures of cellular stress to aid in the identification of novel genes/pathways involved in the cellular response to genotoxic carcinogens.

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Section: Discussionsupporting

confidence: 89%

Time- and concentration-dependent changes in gene expression induced by benzo(a)pyrene in two human cell lines, MCF-7 and HepG2

et al. 2006

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“…Finally, these cells are immortalized and hence may simply lack inducible repair processes. Microarray analysis of HeLa cells that were treated with the genotoxin benzo-[a]pyrene diol-epoxide also did not display alterations in the expression of any of the DNA repair genes analyzed [Yu et al, 2000]. It is also interesting to note that hydrogen peroxide, which not only damages DNA but also other macromolecules, did not alter any genes known to be associated with increased intracellular oxidative stress.…”

Section: Discussionmentioning

confidence: 87%

Identification of transcriptome profiles for the DNA‐damaging agents bleomycin and hydrogen peroxide in L5178Y mouse lymphoma cells

Seidel¹,

Kan²,

Stott³

et al. 2003

Environ and Mol Mutagen

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It is believed that some aspects of genotoxicity are associated with changes in the transcription levels of certain genes, especially those involved in DNA repair and cell cycle control. Additionally, it is hypothesized that chemicals sharing a common mode of genotoxicity should exhibit similar changes in gene expression. We have evaluated these hypotheses by analyzing transcriptome profiles of mouse lymphoma L5178Y/TK(+/-) cells treated with bleomycin and hydrogen peroxide, two mutagens that produce genotoxicity by generating reactive free radicals. The cells were treated for 4 hr and RNA was isolated at the end of the treatment and after a 20 hr recovery. Transcriptome analyses were performed using the Clontech Mouse 1.2K cDNA microarray (1,185 genes) and hybridization with a (32)[P]-labeled probe. Of the genes examined, each mutagen altered the expression (1.5-fold or greater) of only two genes after the 4 hr treatment. In cells allowed to recover for 20 hr after treatment, bleomycin and hydrogen peroxide altered the expression of 8 and 5 genes, respectively. Many of the altered genes have some association with apoptosis. Of these genes, three (the genes encoding granzyme A, integrin beta 7, and 45 kDa calcium-binding protein precursor) were in common between chemical treatments. The expression of DNA repair and cell cycle controlling genes present on the array was not affected by the treatments. These results show that bleomycin and hydrogen peroxide both have unique and commonly regulated genes that have the potential to serve as biomarkers of exposure to agents causing DNA damage by free radical mechanisms.

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“…However, the possibility of direct modification of these transcription factor genes and/or their promoter sequences by DNA damaging agents cannot be eliminated. Further-more, Yu et al [2000] used cDNA expression arrays to identify genes responsive to benzo[␣]pyrene diol epoxide (activated form of benzo[␣]pyrene) in HeLa cells and found that two transcriptional factors, DB1 (zinc finger protein 91) and ETR103 (early growth response protein 1), were upregulated. This observation suggests that the altered expression of transcriptional factors might be a general response to DNA damaging agents.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of zinc finger proteins, ADAMs, and integrin‐related proteins following treatment of cultured human cells with a low concentration of N‐methyl‐N′‐nitro‐N‐nitrosoguanidine

Jin

Gao

Guo

et al. 2003

Environ and Mol Mutagen

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Proteomic analysis is an important approach to characterize the proteome and study protein functions. It is also a powerful screening method for detecting unexpected alterations in protein expression that may be overlooked by conventional biochemical techniques. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) is an alkylating agent that can induce nontargeted mutagenesis in treated cells, although the mechanism remains unclear. Using an efficient proteomic method, we identified several cellular proteins that are responsive to low-concentration MNNG treatment in human FL cells. After MNNG treatment, whole cellular proteins were separated using two-dimensional gel electrophoresis and visualized by silver staining; the digitized images then were analyzed with 2D analysis software. More than 60 proteins showed significant changes in MNNG-treated cells compared to control cells (DMSO treatment). Thirty-one proteins only detected in MNNG-treated or control cells were subjected to in-gel digestion with trypsin and identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry using peptide mass fingerprinting. Eighteen of theses proteins have been identified, including several zinc finger proteins, two members of the ADAMs (a disintegrin and metalloprotease domain) family, and two integrins. Most of these proteins have unknown functions and their involvement in the cellular responses to alkylating agents have not been reported. Therefore, our findings may offer new insights into the mechanisms of low-concentration MNNG-induced nontargeted mutagenesis and these proteins may serve as new biomarkers for detecting exposure of human populations to environmental carcinogens.

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Identification of genes responsive to BPDE treatment in HeLa cells using cDNA expression assays

Cited by 20 publications

References 41 publications

Time- and concentration-dependent changes in gene expression induced by benzo(a)pyrene in two human cell lines, MCF-7 and HepG2

Time- and concentration-dependent changes in gene expression induced by benzo(a)pyrene in two human cell lines, MCF-7 and HepG2

Identification of transcriptome profiles for the DNA‐damaging agents bleomycin and hydrogen peroxide in L5178Y mouse lymphoma cells

Altered expression of zinc finger proteins, ADAMs, and integrin‐related proteins following treatment of cultured human cells with a low concentration of N‐methyl‐N′‐nitro‐N‐nitrosoguanidine

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