Effect of polyaryl hydrocarbons on cytotoxicity in monocytic cells

Potential role of cytochromes P450 and oxidative stress pathways

Sabina Ranjit, Narasimha M. Midde, Namita Sinha, Benjamin J. Patters, Mohammad A. Rahman, Theodore Cory, P. S.S. Rao, Santosh Kumar

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Benzo(a)pyrene (BaP), naphthalene (NPh), phenanthrene (Phe), benzo(a)antharacene (BeA), and benzo(b)fluoranthene (BeF) are known carcinogenic polyaryl hydrocarbons (PAHs) present in cigarette smoke. This study was designed to examine the relative effect of these constituents on the cytotoxicity of monocytic cells and the possible mechanism of PAH-mediated cytotoxicity. Methods: We examined the acute (6-24 hours) and chronic (7 days) effects of these PAHs on the expression of cytochromes P450 (CYPs), oxidative stress, and cytotoxicity. The treated cells were examined for mRNA and protein levels of CYPs (1A1 and 3A4) and antioxidants enzymes (AOEs) superoxide dismutase-1 (SOD1) and catalase. Further, we assessed the levels of reactive oxygen species (ROS), caspase-3 cleavage activity, and cell viability. We performed these experiments in U937 and/or primary monocytic cells. Results: Of the five PAHs tested, after chronic treatment only BaP (100 nM) showed a significant increase in the expression of CYP1A1, AOEs (SOD1 and catalase), ROS generation, caspase-3 cleavage activity, and cytotoxicity. However, acute treatment with BaP showed only an increase in the mRNA expression of CYP1A1. Conclusions: These results suggest that of the five PAHs tested, BaP is the major contributor to the toxic effect of PAHs in monocytic cells, which is likely to occur through CYP and oxidative stress pathways.

Original languageEnglish (US)
Article numbere0163827
JournalPLoS One
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Oxidative stress
Cytotoxicity
Hydrocarbons
cytochrome P-450
Cytochrome P-450 Enzyme System
hydrocarbons
cytotoxicity
Oxidative Stress
oxidative stress
Cytochrome P-450 CYP1A1
cells
caspase-3
Caspase 3
Catalase
Superoxide Dismutase
reactive oxygen species
Reactive Oxygen Species
catalase
superoxide dismutase
Antioxidants

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Effect of polyaryl hydrocarbons on cytotoxicity in monocytic cells : Potential role of cytochromes P450 and oxidative stress pathways. / Ranjit, Sabina; Midde, Narasimha M.; Sinha, Namita; Patters, Benjamin J.; Rahman, Mohammad A.; Cory, Theodore; Rao, P. S.S.; Kumar, Santosh.

In: PLoS One, Vol. 11, No. 9, e0163827, 01.09.2016.

Research output: Contribution to journalArticle

Ranjit, Sabina ; Midde, Narasimha M. ; Sinha, Namita ; Patters, Benjamin J. ; Rahman, Mohammad A. ; Cory, Theodore ; Rao, P. S.S. ; Kumar, Santosh. / Effect of polyaryl hydrocarbons on cytotoxicity in monocytic cells : Potential role of cytochromes P450 and oxidative stress pathways. In: PLoS One. 2016 ; Vol. 11, No. 9.
@article{10b3bfbf517a437aabe69d0ab206bf1f,
title = "Effect of polyaryl hydrocarbons on cytotoxicity in monocytic cells: Potential role of cytochromes P450 and oxidative stress pathways",
abstract = "Background: Benzo(a)pyrene (BaP), naphthalene (NPh), phenanthrene (Phe), benzo(a)antharacene (BeA), and benzo(b)fluoranthene (BeF) are known carcinogenic polyaryl hydrocarbons (PAHs) present in cigarette smoke. This study was designed to examine the relative effect of these constituents on the cytotoxicity of monocytic cells and the possible mechanism of PAH-mediated cytotoxicity. Methods: We examined the acute (6-24 hours) and chronic (7 days) effects of these PAHs on the expression of cytochromes P450 (CYPs), oxidative stress, and cytotoxicity. The treated cells were examined for mRNA and protein levels of CYPs (1A1 and 3A4) and antioxidants enzymes (AOEs) superoxide dismutase-1 (SOD1) and catalase. Further, we assessed the levels of reactive oxygen species (ROS), caspase-3 cleavage activity, and cell viability. We performed these experiments in U937 and/or primary monocytic cells. Results: Of the five PAHs tested, after chronic treatment only BaP (100 nM) showed a significant increase in the expression of CYP1A1, AOEs (SOD1 and catalase), ROS generation, caspase-3 cleavage activity, and cytotoxicity. However, acute treatment with BaP showed only an increase in the mRNA expression of CYP1A1. Conclusions: These results suggest that of the five PAHs tested, BaP is the major contributor to the toxic effect of PAHs in monocytic cells, which is likely to occur through CYP and oxidative stress pathways.",
author = "Sabina Ranjit and Midde, {Narasimha M.} and Namita Sinha and Patters, {Benjamin J.} and Rahman, {Mohammad A.} and Theodore Cory and Rao, {P. S.S.} and Santosh Kumar",
year = "2016",
month = "9",
day = "1",
doi = "10.1371/journal.pone.0163827",
language = "English (US)",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Effect of polyaryl hydrocarbons on cytotoxicity in monocytic cells

T2 - Potential role of cytochromes P450 and oxidative stress pathways

AU - Ranjit, Sabina

AU - Midde, Narasimha M.

AU - Sinha, Namita

AU - Patters, Benjamin J.

AU - Rahman, Mohammad A.

AU - Cory, Theodore

AU - Rao, P. S.S.

AU - Kumar, Santosh

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background: Benzo(a)pyrene (BaP), naphthalene (NPh), phenanthrene (Phe), benzo(a)antharacene (BeA), and benzo(b)fluoranthene (BeF) are known carcinogenic polyaryl hydrocarbons (PAHs) present in cigarette smoke. This study was designed to examine the relative effect of these constituents on the cytotoxicity of monocytic cells and the possible mechanism of PAH-mediated cytotoxicity. Methods: We examined the acute (6-24 hours) and chronic (7 days) effects of these PAHs on the expression of cytochromes P450 (CYPs), oxidative stress, and cytotoxicity. The treated cells were examined for mRNA and protein levels of CYPs (1A1 and 3A4) and antioxidants enzymes (AOEs) superoxide dismutase-1 (SOD1) and catalase. Further, we assessed the levels of reactive oxygen species (ROS), caspase-3 cleavage activity, and cell viability. We performed these experiments in U937 and/or primary monocytic cells. Results: Of the five PAHs tested, after chronic treatment only BaP (100 nM) showed a significant increase in the expression of CYP1A1, AOEs (SOD1 and catalase), ROS generation, caspase-3 cleavage activity, and cytotoxicity. However, acute treatment with BaP showed only an increase in the mRNA expression of CYP1A1. Conclusions: These results suggest that of the five PAHs tested, BaP is the major contributor to the toxic effect of PAHs in monocytic cells, which is likely to occur through CYP and oxidative stress pathways.

AB - Background: Benzo(a)pyrene (BaP), naphthalene (NPh), phenanthrene (Phe), benzo(a)antharacene (BeA), and benzo(b)fluoranthene (BeF) are known carcinogenic polyaryl hydrocarbons (PAHs) present in cigarette smoke. This study was designed to examine the relative effect of these constituents on the cytotoxicity of monocytic cells and the possible mechanism of PAH-mediated cytotoxicity. Methods: We examined the acute (6-24 hours) and chronic (7 days) effects of these PAHs on the expression of cytochromes P450 (CYPs), oxidative stress, and cytotoxicity. The treated cells were examined for mRNA and protein levels of CYPs (1A1 and 3A4) and antioxidants enzymes (AOEs) superoxide dismutase-1 (SOD1) and catalase. Further, we assessed the levels of reactive oxygen species (ROS), caspase-3 cleavage activity, and cell viability. We performed these experiments in U937 and/or primary monocytic cells. Results: Of the five PAHs tested, after chronic treatment only BaP (100 nM) showed a significant increase in the expression of CYP1A1, AOEs (SOD1 and catalase), ROS generation, caspase-3 cleavage activity, and cytotoxicity. However, acute treatment with BaP showed only an increase in the mRNA expression of CYP1A1. Conclusions: These results suggest that of the five PAHs tested, BaP is the major contributor to the toxic effect of PAHs in monocytic cells, which is likely to occur through CYP and oxidative stress pathways.

UR - http://www.scopus.com/inward/record.url?scp=84991628679&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991628679&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0163827

DO - 10.1371/journal.pone.0163827

M3 - Article

VL - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e0163827

ER -