Benzo(a)pyrene-induced apoptotic death of mouse hepatoma Hepa1c1c7 cells via activation of intrinsic caspase cascade and mitochondrial dysfunction

Ko, Chang-Bo; Kim, Se-Jin; Park, Channy; Kim, Bok-Ryang; Shin, Changyong; Choi, Seung-Hee; Chung, Sung Tae; Noh, Ji Heon; Jeun, Jin-Ho; Kim, Nam-Song; Park, Raekil

doi:10.1016/j.tox.2004.01.039

Cited by 58 publications

(43 citation statements)

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“…ROS may have a multifactorial origin, mitochondria being one of the possible sources. Arsenic, a well characterized and common carcinogen, damages mitochondria and promotes mitochondrial ROS production (237,238), and the carcinogen benzo(a)pyrene induces mitochondrial dysfunction (239). Importantly, the accumulation of mutations in people not exposed to carcinogens is associated with the presence of peroxidized lipids.…”

Section: Cancer and Ageing 621 Cancermentioning

confidence: 99%

Mitochondrial dysfunction in human pathologies

Monsalve¹

2007

Front Biosci

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The integrity of mitochondrial function is fundamental to cell life. The cell demands for mitochondria and their complex integration into cell biology, extends far beyond the provision of ATP. It follows that disturbances of mitochondrial function lead to disruption of cell function, expressed as disease or even death. Mitochondria are major producers of free radical species and also possibly of nitric oxide, and are, at the same time, major targets for oxidative damage. In this review we consider recent developments in our knowledge of how the mitochondrial production of reactive oxygen species (ROS) plays a critical role in several major human pathologies. We will also consider recent advances in our understanding of the molecular mechanisms involved in mitochondrial ROS detoxification.

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Section: Cancer and Ageing 621 Cancermentioning

confidence: 99%

Mitochondrial dysfunction in human pathologies

Monsalve¹

2007

Front Biosci

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“…The decreasing total counts of erythrocytes in the peripheral blood of animals treated with 1.0 mg/kg (Ko et al, 2004) and/or its metabolites on bone marrow (Yoon et al, 2001). The decrease in numbers of erythrocytes was associated with decreased body weight because the animals in the group receiving 10.0 mg/kg of B[a]P were significantly lighter.…”

Section: Discussionmentioning

confidence: 99%

Effects of postnatal exposure to benzo[a]pyrene on the immunity of immature rats

Matiašovic¹,

Levá²,

Mašková³

et al. 2008

Vet. Med. - Czech

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ABSTRACT:To determine the effect of benzo [a]pyrene (B[a]P) on the developing immune system of immature rats, newborn animals received different concentrations (0.1, 1.0 and 10.0 mg/kg/day) of B[a]P in the first 14 days after birth. These rats were euthanised on day 23 of the experiment and it was found that the decreasing numbers of erythrocytes were in direct correlation to the dose of B[a]P. In subject animals, the overall counts of T cells in the spleen and the mitogenic activity increased. A decrease in the production of both IFN-γ and IL-4 (measured at the mRNA level) as well as the decreasing IFN-γ/IL-4 ratio in rat splenocytes were dependent on the dose of B[a]P. From this we may deduce that exposure to B[a]P in immature animals may modulate the immune response to infection and/or vaccination. Keywords: polycyclic aromatic hydrocarbons; immunity; IFN-γ; IL-4; cytokinesPolycyclic aromatic hydrocarbons (PAHs) are mostly anthropogenic in origin and are released both as a result of incomplete combustion in coal, oil, gasoline and wood and in consequence of some other pyrolytic processes (Motelay-Massei et al., 2007). Benzo [a]pyrene (B[a]P) is widely used as a prototypical PAH which exhibits significant genotoxicity and negative effects on different components of the immune system. The impact of B[a]P on the immune system varies from reduced humoral immunity to increased T cell mitogenic activity (Davila et al., 1996;Burchiel and Luster, 2001;Burchiel et al., 2004 (Harper et al., 1996).In earlier studies, it was the toxic effects of B[a]P that were mainly described and decreases in humoral and cell-mediated immunity were documented (Ward et al., 1984;Dean et al., 1986). The differences in the sensitivity of humans and rodents to varying doses of B[a]P were also described and the observation that humans were 10-100 times more sensitive to toxic effects of B[a]P than rodents was made (Davila et al., 1996). Depending on their doses, different fractions of the reconstituted PAH mixture show different effect on the humoral and cell-mediated immunity in mouse splenocytes (Harper et al., 1996). Interestingly, in more recent studies, signs of a possible adjuvant effect of PAHs or DE were shown. For example, increasing in vitro mitogenic activity of mouse spleen T cells in the presence of 1 µM B[a]P was documented (Burchiel et al., 2004). Also Fujimaki et al. (2001) found an increasing production of IFN-γ but not IL-4 and IL-5 by splenocytes in mice exposed to DE. In contrast, the work of Diaz-Sanchez et al. (1997) showed a decreased expression of mRNA for Th1-type cytokines (IFN-γ and IL-2) but an elevated expression for other cytokines (IL-4, 5, 6, 10, and 13) in human cells isolated from nasal lavages after stimulation by ragweed allergens and exposure to DE particles. The mechanism of this effect is not clear, but seems to be complex due to possible interaction between PAH metabolites and different lymphocyte signalling pathways such as the aryl hydrocarbon

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“…rat Sertoli cells (Raychoudhury & Kubinski, 2003), mouse hepatoma Hepa1c1c7 cells (Ko et al, 2004) and human HepG2 cells . There are many ways to apoptosis and benzo [a]pyrene may affect different apoptotic pathways in different cell types.…”

Section: Effects On Apoptosismentioning

confidence: 99%

“…Mouse embryo fibroblasts null for p38 were resistant to the apoptotic effect of the latter. In Hepa1c1c7 cells, Ko et al (2004) showed that catalytic activation of caspases 3 and 9 by benzo [a]pyrene was associated with cytosolic release of cytochrome c, a decrease in B-cell lymphoma protein 2 (Bcl-2) to Bcl-2-antagonist X protein (Bax) ratio and ser-15 phosphorylation of p53. Benzo [a]pyrene and its 7,8-dihydrodiol and diol epoxide metabolites induced apoptosis and phosphorylation of p53 in mouse hepatoma Hepa1c1c7 cells, while benzo [a]pyrene-4,5-dihydrodiol did not.…”

Section: Effects On Apoptosismentioning

confidence: 99%

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

Hellou¹,

Beach²,

Leonard³

et al. 2012

Polycyclic Aromatic Compounds

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initiated a programme on the evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, life-style factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate and publish in the form of monographs critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations; to evaluate these data in terms of human risk with the help of international working groups of experts in chemical carcinogenesis Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved.The International Agency for Research on Cancer welcomes requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce or translate IARC publications -whether for sale or for noncommercial distribution -should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; email: permissions@who.int).The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.The IARC Monographs Working Group alone is responsible for the views expressed in this publication. IARC Library Cataloguing in Publication Data NOTE TO THE READERThe term 'carcinogenic risk' in the IARC Monographs series is taken to mean that an agent is capable of causing cancer under some circumstances. The Monographs evaluate cancer hazards, despite the historical presence of the word 'risks' in the title.Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the published data have been examined. Equally, the fact that an agent has not yet been evaluated in a Monograph does not mean that it is not carcinogenic.The evaluations of carcinogenic risk are made by international working groups of independent scientists and are qualitative in nature. No recommendation is given for regulation or legislation.Anyone who is aware of published data that may alter the evaluation of the carcinogenic risk of an agent to humans is encouraged to make this information available to the Section of IARC Monographs, International Agency for...

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Benzo(a)pyrene-induced apoptotic death of mouse hepatoma Hepa1c1c7 cells via activation of intrinsic caspase cascade and mitochondrial dysfunction

Cited by 58 publications

References 31 publications

Mitochondrial dysfunction in human pathologies

Mitochondrial dysfunction in human pathologies

Effects of postnatal exposure to benzo[a]pyrene on the immunity of immature rats

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

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