DNA reactions, mutagenic action and stealth properties of polycyclic aromatic hydrocarbon carcinogens (review).

Dipple, Anthony; Khan, Qasim; Page, John E.; Pontén, Ingrid; Szeliga, Jan

doi:10.3892/ijo.14.1.103

Cited by 56 publications

(57 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2A). The inability of BaP treatment to affect p21 WAF1 expression was not unexpected, since studies published elsewhere have reported that bypassing p21 WAF1 tumor suppressor functions is a characteristic of the stealth nature of cigarette smoke carcinogens, by which the carcinogens induce DNA damage and propagate mutations without inducing cell cycle arrest (20,35,36). However, in the current study, the observed lack of p21 WAF1 induction with BaP could also be due to the HPV E6 oncoprotein targeting of p53 functions.…”

Section: Resultscontrasting

confidence: 52%

Downregulation of Cdc2/CDK1 Kinase Activity Induces the Synthesis of Noninfectious Human Papillomavirus Type 31b Virions in Organotypic Tissues Exposed to Benzo[ a ]pyrene

Alam

Bowser

Conway

et al. 2010

J Virol

View full text Add to dashboard Cite

Epidemiological studies suggest that human papillomavirus (HPV)-infected women who smoke face an increased risk for developing cervical cancer. We have previously reported that exposure of HPV-positive organotypic cultures to benzo[a]pyrene (BaP), a major carcinogen in cigarette smoke, resulted in enhanced viral titers. Since BaP is known to deregulate multiple pathways of cellular proliferation, enhanced virion synthesis could result from carcinogen/host cell interaction. Here, we report that BaP-mediated upregulation of virus synthesis is correlated to an altered balance between cell cycle-specific cyclin-dependent kinase (CDK) activity profile compared with controls. Specifically, BaP treatment increased accumulation of hyperphosphorylated retinoblastoma protein (pRb) which coincided with increased cdc2/CDK1 kinase activity, but which further conflicted with the simultaneous upregulation of CDK inhibitors p16 INK4 and p27 KIP1 , which normally mediate pRb hypophosphorylation. In contrast, p21 WAF1 and p53 levels remained unchanged. Under these conditions, CDK6 and CDK2 kinase activities were decreased, whereas CDK4 kinase activity remained unchanged. The addition of purvalanol A, a specific inhibitor of CDK1 kinase, to BaP-treated cultures, resulted in the production of noninfectious HPV type 31b (HPV31b) particles. In contrast, infectivity of control virus was unaffected by purvalanol A treatment. BaP targeting of CDK1 occurred independently of HPV status, since BaP treatment also increased CDK1 activity in tissues derived from primary keratinocytes. Our data indicate that HPV31b virions synthesized in the presence of BaP were dependent on BaP-mediated alteration in CDK1 kinase activity for maintaining their infectivity.

show abstract

Section: Resultscontrasting

confidence: 52%

Downregulation of Cdc2/CDK1 Kinase Activity Induces the Synthesis of Noninfectious Human Papillomavirus Type 31b Virions in Organotypic Tissues Exposed to Benzo[ a ]pyrene

Alam

Bowser

Conway

et al. 2010

J Virol

View full text Add to dashboard Cite

show abstract

“…Indeed, all CYPs relevant for ellipticine metabolism (CYP1A1, 1B1 and 3A4) were found to be expressed both at mRNA and protein levels. A number of DNA-damaging agents have been shown to inhibit cell growth by arrest at the G1/S boundary of the cell cycle [47][48][49]. This cell arrest is thought to be an important cellular defense mechanism that prevents replication of damaged DNA.…”

Section: Discussionmentioning

confidence: 99%

The mechanism of cytotoxicity and DNA adduct formation by the anticancer drug ellipticine in human neuroblastoma cells

Poljaková

Eckschlager

Hraběta

et al. 2009

Biochemical Pharmacology

View full text Add to dashboard Cite

Ellipticine is an antineoplastic agent, whose mode of action is based mainly on DNA intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts mediated by cytochromes P450 and peroxidases. Here, the molecular mechanism of DNA-mediated ellipticine action in human neuroblastoma IMR-32, UKF-NB-3 and UKF-NB-4 cancer cell lines was investigated. Treatment of neuroblastoma cells with ellipticine resulted in apoptosis induction, which was verified by the appearance of DNA fragmentation, and in inhibition of cell growth. These effects were associated with formation of two covalent ellipticine-derived DNA adducts, identical to those formed by the cytochrome P450-and peroxidase-mediated ellipticine metabolites, 13-hydroxy-and 12-hydroxyellipticine. The expression of these enzymes at mRNA and protein levels and their ability to generate ellipticine-DNA adducts in neuroblastoma cells were proven, using the real-time polymerase chain reaction, Western blotting analyses and by analyzing ellipticine-DNA adducts in incubations of this drug with neuroblastoma S9 fractions, enzyme cofactors and DNA. The levels of DNA adducts correlated with toxicity of ellipticine to IMR-32 and UKF-NB-4 cells, but not with that to UKF-NB-3 cells. In addition, hypoxic cell culture conditions resulted in a decrease in ellipticine toxicity to IMR-32 and UKF-NB-4 cells and this correlated with lower levels of DNA adducts. Both these cell lines accumulated in S phase, suggesting that ellipticine-DNA adducts interfere with DNA replication. The results demonstrate that among the multiple modes of ellipticine antitumor action, formation of covalent DNA adducts by ellipticine is the predominant mechanism of cytotoxicity to IMR-32 and UKF-NB-4 neuroblastoma cells.

show abstract

“…Some of these compounds e.g. Benzo (a) Pyrene have been classified as carcinogenic and mutagenic materials (Dipple et al, 1999;Wei et al, 1996). PAHs compounds are extracted from the filter with a solvent and analyzed by high performance liquid chromatography with a fluorescence detector or gas chromatography with a flame ionization detector, or gas chromatography-mass spectrometry (Hansen et al, 1991;Dabek-Zlotorzynska et al, 1996, Marvin et al, 1999Soltanali and Shams Hagani, 2008).…”

Section: Introductionmentioning

confidence: 99%

Distribution behavior of polycyclic aromatic hydrocarbons in roadside soil at traffic intercepts within developing cities

Kumar

Kothiyal

2010

Int. J. Environ. Sci. Technol.

View full text Add to dashboard Cite

A study of polycyclic aromatic hydrocarbons pollution in roadside soil was conducted in developing city environment of northern India during autumn and winter season to ascertain the contamination levels and their distribution behavior in soil. The concentration of polycyclic aromatic hydrocarbons was determined at ten locations of Jalandhar city, Punjab in India at 1, 2 and 3 m distances from roadside in soil covering all the major traffic intercepts within city. The samples were extracted in acetone and dichloromethane (1:1) using soxhlet extraction. The extracts were then filtered on a silica gel micro column to remove impurities and elute was subjected to GC-FID. The total average concentration (city average) was found to be 4.04 µg/g and 16.38 µg/g during winter and autumn respectively. DiBenzo (ah) Anthracene and Benzo (a) Pyrene were the individual polycyclic aromatic hydrocarbons found in highest concentration at all the intercepts ranging between 0.008 to 28.4 µg/g during winter and 0.01 to 252.55 µg/g during autumn. Average concentration of non-carcinogenic and carcinogenic polycyclic aromatic hydrocarbons during winter and autumn was found to be 2.1 and 6.4 and 4.74 and 35.08 µg/g respectively. The average ratio of non-carcinogenic and carcinogenic Polycyclic Aromatic Hydrocarbons was found to be 1:3 during winter, and 1:7.6 during autumn at most of the intercepts. Total carcinogenic polycyclic aromatic hydrocarbons concentration was found quite high (80 %) in comparison to non-carcinogenic polycyclic aromatic hydrocarbons (20 %) at most of the intercepts.

show abstract

DNA reactions, mutagenic action and stealth properties of polycyclic aromatic hydrocarbon carcinogens (review).

Cited by 56 publications

References 0 publications

Downregulation of Cdc2/CDK1 Kinase Activity Induces the Synthesis of Noninfectious Human Papillomavirus Type 31b Virions in Organotypic Tissues Exposed to Benzo[ a ]pyrene

Downregulation of Cdc2/CDK1 Kinase Activity Induces the Synthesis of Noninfectious Human Papillomavirus Type 31b Virions in Organotypic Tissues Exposed to Benzo[ a ]pyrene

The mechanism of cytotoxicity and DNA adduct formation by the anticancer drug ellipticine in human neuroblastoma cells

Distribution behavior of polycyclic aromatic hydrocarbons in roadside soil at traffic intercepts within developing cities

Contact Info

Product

Resources

About