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Bisphenol a promotes cell survival following oxidative DNA damage in mouse fibroblasts.

Gassman NR, Coskun E, Stefanick DF, Horton JK, Jaruga P, Dizdaroglu M, Wilson SH - PLoS ONE (2015)

Bottom Line: Yet, the relationship between BPA and BER has yet to be examined.To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3) or laser irradiation as oxidative damaging agents.In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA.

View Article: PubMed Central - PubMed

Affiliation: Genomic Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States of America.

ABSTRACT
Bisphenol A (BPA) is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER) is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal endogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3) or laser irradiation as oxidative damaging agents. In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway.

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Strand break signaling by γH2AX in Ku70-deficient cells.γH2AX foci were measured at 4 h after exposure to BPA alone, KBrO3 alone, and after co-exposure (see Material and Methods). Each bar represents mean ± SEM of three independent experiments (*p < 0.05 vs. control).
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pone.0118819.g004: Strand break signaling by γH2AX in Ku70-deficient cells.γH2AX foci were measured at 4 h after exposure to BPA alone, KBrO3 alone, and after co-exposure (see Material and Methods). Each bar represents mean ± SEM of three independent experiments (*p < 0.05 vs. control).

Mentions: To determine if BPA and KBrO3 co-treatment altered the levels of oxidatively induced DNA base lesions, we quantified five oxidatively induced DNA lesions in DNA isolated from Ku70-deficient cells treated with BPA alone, KBrO3 alone, or co-treated with BPA and KBrO3 (Table 1). GC-MS/MS with isotope-dilution, as described [26], was used with nuclear DNA isolated from untreated control cells or treated cells 4 h after treatment. The results are shown in Table 1 and summarized in Fig. 4.


Bisphenol a promotes cell survival following oxidative DNA damage in mouse fibroblasts.

Gassman NR, Coskun E, Stefanick DF, Horton JK, Jaruga P, Dizdaroglu M, Wilson SH - PLoS ONE (2015)

Strand break signaling by γH2AX in Ku70-deficient cells.γH2AX foci were measured at 4 h after exposure to BPA alone, KBrO3 alone, and after co-exposure (see Material and Methods). Each bar represents mean ± SEM of three independent experiments (*p < 0.05 vs. control).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4334494&req=5

pone.0118819.g004: Strand break signaling by γH2AX in Ku70-deficient cells.γH2AX foci were measured at 4 h after exposure to BPA alone, KBrO3 alone, and after co-exposure (see Material and Methods). Each bar represents mean ± SEM of three independent experiments (*p < 0.05 vs. control).
Mentions: To determine if BPA and KBrO3 co-treatment altered the levels of oxidatively induced DNA base lesions, we quantified five oxidatively induced DNA lesions in DNA isolated from Ku70-deficient cells treated with BPA alone, KBrO3 alone, or co-treated with BPA and KBrO3 (Table 1). GC-MS/MS with isotope-dilution, as described [26], was used with nuclear DNA isolated from untreated control cells or treated cells 4 h after treatment. The results are shown in Table 1 and summarized in Fig. 4.

Bottom Line: Yet, the relationship between BPA and BER has yet to be examined.To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3) or laser irradiation as oxidative damaging agents.In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA.

View Article: PubMed Central - PubMed

Affiliation: Genomic Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States of America.

ABSTRACT
Bisphenol A (BPA) is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER) is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal endogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3) or laser irradiation as oxidative damaging agents. In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway.

Show MeSH
Related in: MedlinePlus