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Arsenite enhances the benzo[a]pyrene diol epoxide (BPDE)-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts in human lung cells.
Toxicol In Vitro. 2009 Aug; 23(5):897-905.TV

Abstract

Arsenite effects on the benzo[a]pyrene diol epoxide (BPDE)-DNA adduct-induced mutation were evaluated in three human lung cell-lines--A549 (wild-type p53), WI38-VA13 (p53 inhibited by SV40 large-T antigen), and H1299 (p53-null)--by using the pSP189 shuttle vector, which carries a mutation target supF gene. Arsenite alone had no significant effect on the spontaneous supF mutation. BPDE modification of pSP189 enhanced the mutation rates of supF 4.37-fold, 2.96-fold, and 1.95-fold for A549, WI38-VA13, and H1299, respectively. Arsenite potentiated the BPDE-induced mutation rates of supF 2.30-fold, 2.31-fold, and 2.35-fold in A549, WI38-VA13, and H1299, respectively. These results suggest that arsenite potentiates the BPDE-induced supF mutation via a p53-independent mechanism. By using the host cell reactivation assay, we evaluated arsenite effect on repair of BPDE-DNA adducts. We found that the arsenite treatments resulting in relative survival rates 65% had no significant effect on repair of BPDE-DNA adducts, indicating that p53 status did not significantly affect the repair of BPDE-DNA adducts. This study reveals that arsenite enhances the BPDE-DNA adduct-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts, suggesting that arsenic may act as a co-mutagen to promote the development of human lung cancer.

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Authors+Show Affiliations

Chiang HC
Laboratory of Molecular Toxicology, Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan.
Tsou TC
No affiliation info available

MeSH

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideArsenitesCell LineCell Line, TumorDNA AdductsDrug SynergismGenes, SuppressorHumansLungLung NeoplasmsMutagenesisMutagensMutationRNA, TransferSodium CompoundsTumor Suppressor Protein p53

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19470404

Citation

Chiang, Huai-Chih, and Tsui-Chun Tsou. "Arsenite Enhances the Benzo[a]pyrene Diol Epoxide (BPDE)-induced Mutagenesis With No Marked Effect On Repair of BPDE-DNA Adducts in Human Lung Cells." Toxicology in Vitro : an International Journal Published in Association With BIBRA, vol. 23, no. 5, 2009, pp. 897-905.
Chiang HC, Tsou TC. Arsenite enhances the benzo[a]pyrene diol epoxide (BPDE)-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts in human lung cells. Toxicol In Vitro. 2009;23(5):897-905.
Chiang, H. C., & Tsou, T. C. (2009). Arsenite enhances the benzo[a]pyrene diol epoxide (BPDE)-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts in human lung cells. Toxicology in Vitro : an International Journal Published in Association With BIBRA, 23(5), 897-905. https://doi.org/10.1016/j.tiv.2009.05.009
Chiang HC, Tsou TC. Arsenite Enhances the Benzo[a]pyrene Diol Epoxide (BPDE)-induced Mutagenesis With No Marked Effect On Repair of BPDE-DNA Adducts in Human Lung Cells. Toxicol In Vitro. 2009;23(5):897-905. PubMed PMID: 19470404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arsenite enhances the benzo[a]pyrene diol epoxide (BPDE)-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts in human lung cells. AU - Chiang,Huai-Chih, AU - Tsou,Tsui-Chun, Y1 - 2009/05/24/ PY - 2009/01/23/received PY - 2009/05/01/revised PY - 2009/05/18/accepted PY - 2009/5/28/entrez PY - 2009/5/28/pubmed PY - 2009/10/14/medline SP - 897 EP - 905 JF - Toxicology in vitro : an international journal published in association with BIBRA JO - Toxicol In Vitro VL - 23 IS - 5 N2 - Arsenite effects on the benzo[a]pyrene diol epoxide (BPDE)-DNA adduct-induced mutation were evaluated in three human lung cell-lines--A549 (wild-type p53), WI38-VA13 (p53 inhibited by SV40 large-T antigen), and H1299 (p53-null)--by using the pSP189 shuttle vector, which carries a mutation target supF gene. Arsenite alone had no significant effect on the spontaneous supF mutation. BPDE modification of pSP189 enhanced the mutation rates of supF 4.37-fold, 2.96-fold, and 1.95-fold for A549, WI38-VA13, and H1299, respectively. Arsenite potentiated the BPDE-induced mutation rates of supF 2.30-fold, 2.31-fold, and 2.35-fold in A549, WI38-VA13, and H1299, respectively. These results suggest that arsenite potentiates the BPDE-induced supF mutation via a p53-independent mechanism. By using the host cell reactivation assay, we evaluated arsenite effect on repair of BPDE-DNA adducts. We found that the arsenite treatments resulting in relative survival rates 65% had no significant effect on repair of BPDE-DNA adducts, indicating that p53 status did not significantly affect the repair of BPDE-DNA adducts. This study reveals that arsenite enhances the BPDE-DNA adduct-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts, suggesting that arsenic may act as a co-mutagen to promote the development of human lung cancer. SN - 1879-3177 UR - https://www.unboundmedicine.com/medline/citation/19470404/Arsenite_enhances_the_benzo[a]pyrene_diol_epoxide__BPDE__induced_mutagenesis_with_no_marked_effect_on_repair_of_BPDE_DNA_adducts_in_human_lung_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0887-2333(09)00113-1 DB - PRIME DP - Unbound Medicine ER -
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