Home > Research > Publications & Outputs > Enhanced micronucleus formation and modulation ...
View graph of relations

Enhanced micronucleus formation and modulation of Bcl-2 : Bax in MCF-7 cells after exposure to binary mixtures.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published

Standard

Enhanced micronucleus formation and modulation of Bcl-2 : Bax in MCF-7 cells after exposure to binary mixtures. / Hewitt, Rebecca; Forero, Albert; Luncsford, Paz J. et al.
In: Environmental Health Perspectives, Vol. 115, No. Supple, 2007, p. 129-136.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Hewitt, R, Forero, A, Luncsford, PJ & Martin, FL 2007, 'Enhanced micronucleus formation and modulation of Bcl-2 : Bax in MCF-7 cells after exposure to binary mixtures.', Environmental Health Perspectives, vol. 115, no. Supple, pp. 129-136. https://doi.org/10.1289/ehp.9361

APA

Hewitt, R., Forero, A., Luncsford, P. J., & Martin, F. L. (2007). Enhanced micronucleus formation and modulation of Bcl-2 : Bax in MCF-7 cells after exposure to binary mixtures. Environmental Health Perspectives, 115(Supple), 129-136. https://doi.org/10.1289/ehp.9361

Vancouver

Hewitt R, Forero A, Luncsford PJ, Martin FL. Enhanced micronucleus formation and modulation of Bcl-2 : Bax in MCF-7 cells after exposure to binary mixtures. Environmental Health Perspectives. 2007;115(Supple):129-136. doi: 10.1289/ehp.9361

Author

Hewitt, Rebecca ; Forero, Albert ; Luncsford, Paz J. et al. / Enhanced micronucleus formation and modulation of Bcl-2 : Bax in MCF-7 cells after exposure to binary mixtures. In: Environmental Health Perspectives. 2007 ; Vol. 115, No. Supple. pp. 129-136.

Bibtex

@article{9b11331a2db34002ae465428fb224446,
title = "Enhanced micronucleus formation and modulation of Bcl-2 : Bax in MCF-7 cells after exposure to binary mixtures.",
abstract = "Background: Within mixtures, interactions between different xenobiotics may occur to give rise to additive, synergistic, inhibitory and/or stimulatory effects in target cells. The role that xenobiotics individually or in mixtures, and at environmental concentrations, play in the etiology of common human diseases often remains obscure. Methods: In the presence or absence of lindane, chromosomal aberrations were detected in MCF-7 cells after 24-hr treatment with benzo[a]pyrene (B[a]P) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using the cytokinesis-block micronucleus assay. Micronuclei were scored in 1,000 binucleate cells/treatment. We investigated intracellular responses using quantitative gene expression analyses of cyclin-dependent kinase inhibitor 1A [CDKN1A (P21WAF1/CIP1) ], B-cell leukemia/lymphoma 2 (BCL-2) , BCL-2–associated X (BAX) , and isoforms of cytochrome P450 (CYP) , CYP1A1, CYP1A2, and CYP1B1. Immunocytochemical analyses of p53, p21Waf1/Cip1, Bcl-2 and Bax protein expression in MCF-7 cells were also carried out. Results: After exposure to binary mixtures of B[a]P plus lindane or PhIP plus lindane, a 10-fold increase in micronucleus formation resulted ; these test agents individually induced 2- to 5-fold increases. Lindane increased the ratio of Bcl-2:Bax, as did 17β-estradiol (E2) . Although treatment with B[a]P alone was found to elevate expression of P21WAF1/CIP1and CYP isoenzymes, it reduced the ratio of BCL-2:BAX mRNA transcripts. Treatment with a binary mixture of 10–8 M B[a]P plus 10–12 M lindane or 10–10 M E2 reversed B[a]P-induced reductions in the ratio of Bcl-2– to Bax-positive cells. In contrast, treatments with PhIP (known to possess hormonelike properties) plus lindane or E2 resulted in profound reductions in Bcl-2:Bax ratio. Conclusions: Our results suggest that low-dose treatments (i.e., close to environmental levels) may increase DNA damage while influencing survival in exposed cells and that these effects may depend on the endocrine activity of test agents.",
keywords = "17β-estradiol, BAX, Bcl-2, benzo[a]pyrene, binary mixture, clonogenic assay, cytokinesis-block micronucleus assay, lindane, micronucleus, PhIP.",
author = "Rebecca Hewitt and Albert Forero and Luncsford, {Paz J.} and Martin, {Frank L.}",
year = "2007",
doi = "10.1289/ehp.9361",
language = "English",
volume = "115",
pages = "129--136",
journal = "Environmental Health Perspectives",
issn = "0091-6765",
publisher = "Public Health Services, US Dept of Health and Human Services",
number = "Supple",

}

RIS

TY - JOUR

T1 - Enhanced micronucleus formation and modulation of Bcl-2 : Bax in MCF-7 cells after exposure to binary mixtures.

AU - Hewitt, Rebecca

AU - Forero, Albert

AU - Luncsford, Paz J.

AU - Martin, Frank L.

PY - 2007

Y1 - 2007

N2 - Background: Within mixtures, interactions between different xenobiotics may occur to give rise to additive, synergistic, inhibitory and/or stimulatory effects in target cells. The role that xenobiotics individually or in mixtures, and at environmental concentrations, play in the etiology of common human diseases often remains obscure. Methods: In the presence or absence of lindane, chromosomal aberrations were detected in MCF-7 cells after 24-hr treatment with benzo[a]pyrene (B[a]P) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using the cytokinesis-block micronucleus assay. Micronuclei were scored in 1,000 binucleate cells/treatment. We investigated intracellular responses using quantitative gene expression analyses of cyclin-dependent kinase inhibitor 1A [CDKN1A (P21WAF1/CIP1) ], B-cell leukemia/lymphoma 2 (BCL-2) , BCL-2–associated X (BAX) , and isoforms of cytochrome P450 (CYP) , CYP1A1, CYP1A2, and CYP1B1. Immunocytochemical analyses of p53, p21Waf1/Cip1, Bcl-2 and Bax protein expression in MCF-7 cells were also carried out. Results: After exposure to binary mixtures of B[a]P plus lindane or PhIP plus lindane, a 10-fold increase in micronucleus formation resulted ; these test agents individually induced 2- to 5-fold increases. Lindane increased the ratio of Bcl-2:Bax, as did 17β-estradiol (E2) . Although treatment with B[a]P alone was found to elevate expression of P21WAF1/CIP1and CYP isoenzymes, it reduced the ratio of BCL-2:BAX mRNA transcripts. Treatment with a binary mixture of 10–8 M B[a]P plus 10–12 M lindane or 10–10 M E2 reversed B[a]P-induced reductions in the ratio of Bcl-2– to Bax-positive cells. In contrast, treatments with PhIP (known to possess hormonelike properties) plus lindane or E2 resulted in profound reductions in Bcl-2:Bax ratio. Conclusions: Our results suggest that low-dose treatments (i.e., close to environmental levels) may increase DNA damage while influencing survival in exposed cells and that these effects may depend on the endocrine activity of test agents.

AB - Background: Within mixtures, interactions between different xenobiotics may occur to give rise to additive, synergistic, inhibitory and/or stimulatory effects in target cells. The role that xenobiotics individually or in mixtures, and at environmental concentrations, play in the etiology of common human diseases often remains obscure. Methods: In the presence or absence of lindane, chromosomal aberrations were detected in MCF-7 cells after 24-hr treatment with benzo[a]pyrene (B[a]P) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using the cytokinesis-block micronucleus assay. Micronuclei were scored in 1,000 binucleate cells/treatment. We investigated intracellular responses using quantitative gene expression analyses of cyclin-dependent kinase inhibitor 1A [CDKN1A (P21WAF1/CIP1) ], B-cell leukemia/lymphoma 2 (BCL-2) , BCL-2–associated X (BAX) , and isoforms of cytochrome P450 (CYP) , CYP1A1, CYP1A2, and CYP1B1. Immunocytochemical analyses of p53, p21Waf1/Cip1, Bcl-2 and Bax protein expression in MCF-7 cells were also carried out. Results: After exposure to binary mixtures of B[a]P plus lindane or PhIP plus lindane, a 10-fold increase in micronucleus formation resulted ; these test agents individually induced 2- to 5-fold increases. Lindane increased the ratio of Bcl-2:Bax, as did 17β-estradiol (E2) . Although treatment with B[a]P alone was found to elevate expression of P21WAF1/CIP1and CYP isoenzymes, it reduced the ratio of BCL-2:BAX mRNA transcripts. Treatment with a binary mixture of 10–8 M B[a]P plus 10–12 M lindane or 10–10 M E2 reversed B[a]P-induced reductions in the ratio of Bcl-2– to Bax-positive cells. In contrast, treatments with PhIP (known to possess hormonelike properties) plus lindane or E2 resulted in profound reductions in Bcl-2:Bax ratio. Conclusions: Our results suggest that low-dose treatments (i.e., close to environmental levels) may increase DNA damage while influencing survival in exposed cells and that these effects may depend on the endocrine activity of test agents.

KW - 17β-estradiol

KW - BAX

KW - Bcl-2

KW - benzo[a]pyrene

KW - binary mixture

KW - clonogenic assay

KW - cytokinesis-block micronucleus assay

KW - lindane

KW - micronucleus

KW - PhIP.

U2 - 10.1289/ehp.9361

DO - 10.1289/ehp.9361

M3 - Journal article

VL - 115

SP - 129

EP - 136

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - Supple

ER -