• Klíčová slova
• CANCER/etiology and pathogenesis *,
• MeSH
• karcinogeneze * MeSH
• lidé MeSH
• nádory etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

• MeSH
• karcinogeneze chemicky indukované   MeSH
• karcinogeny životního prostředí škodlivé účinky   MeSH
• lidé MeSH
• nádory chemicky indukované   etiologie   MeSH
• nebezpečné látky škodlivé účinky   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• karcinogeny životního prostředí MeSH
• nebezpečné látky MeSH

In the present review we addressed the determination of DNA damage induced by small-molecule carcinogens, considered their persistence in DNA and mutagenicity in in vitro and in vivo systems over a period of 30 years. The review spans from the investigation of the role of DNA damage in the cascade of chemical carcinogenesis. In the nineties, this concept evolved into the biomonitoring studies comprising multiple biomarkers that not only reflected DNA/chromosomal damage, but also the potential of the organism for biotransformation/elimination of various xenobiotics. Since first years of the new millennium, dynamic system of DNA repair and host susceptibility factors started to appear in studies and a considerable knowledge has been accumulated on carcinogens and their role in carcinogenesis. It was understood that the final biological links bridging the arising DNA damage and cancer onset remain to be elucidated. In further years the community of scientists learnt that cancer is a multifactorial disease evolving over several decades of individual´s life. Moreover, DNA damage and DNA repair are inseparable players also in treatment of malignant diseases, but affect substantially other processes, such as degeneration. Functional monitoring of DNA repair pathways and DNA damage response may cast some light on above aspects. Very little is currently known about the relationship between telomere homeostasis and DNA damage formation and repair. DNA damage/repair in genomic and mitochondrial DNA and crosstalk between these two entities emerge as a new interesting topic.

• Klíčová slova
• Butadiene, DNA damage, DNA repair, Formaldehyde, Occupational medicine, Styrene,
• MeSH
• DNA MeSH
• karcinogeneze genetika   MeSH
• karcinogeny MeSH
• kometový test MeSH
• lidé MeSH
• oprava DNA MeSH
• poškození DNA MeSH
• pracovní expozice * MeSH
• xenobiotika * toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• DNA MeSH
• karcinogeny MeSH
• xenobiotika * MeSH

The role of immune system in carcinogenesis represents fundamental events associated with cancer eradication; however, tumor evolution is connected with various mechanisms of tumor evasion and progression of cancer. Based on recent evidence, phytochemicals are directly associated with immunomodulation of the innate and adaptive immunity via different mechanisms of action including stimulation and amplification of immune cells, humoral compartments, and associated molecules. This comprehensive study focuses on immunomodulating potential of phytochemicals (mixture in plants or separately such as individual phytochemical) and their impact on regulation of immune response during cancer development, immune tolerance, and immune escape. Clinical application of phytochemicals as modulators of host immunity against cancer may represent perspective approach in anticancer therapy.

• Klíčová slova
• Cancer, Cytokines, Immunomodulation, Phytochemicals, Preclinical and clinical research,
• MeSH
• fytonutrienty terapeutické užití   MeSH
• imunologická tolerance účinky léků   MeSH
• imunomodulace účinky léků   MeSH
• karcinogeneze účinky léků   MeSH
• lidé MeSH
• nádory farmakoterapie   patologie   MeSH
• přirozená imunita účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fytonutrienty MeSH

Health-threatening consequences of carcinogen exposure are mediated via occurrence of electrophiles or reactive oxygen species. As a result, the accumulation of biomolecular damage leads to the cancer initiation, promotion or progression. Accordingly, there is an association between lifestyle factors including inappropriate diet or carcinogen formation during food processing, mainstream, second or third-hand tobacco smoke and other environmental or occupational carcinogens and malignant transformation. Nevertheless, increasing evidence supports the protective effects of naturally occurring phytochemicals against carcinogen exposure as well as carcinogenesis in general. Isolated phytochemicals or their mixtures present in the whole plant food demonstrate efficacy against malignancy induced by carcinogens widely spread in our environment. Phytochemicals also minimize the generation of carcinogenic substances during the processing of meat and meat products. Based on numerous data, selected phytochemicals or plant foods should be highly recommended to become a stable and regular part of the diet as the protectors against carcinogenesis.

• Klíčová slova
• Antioxidant, Carcinogens, Chemoprevention, Detoxification, Dietary phytochemicals, Metabolic activation, Scavenging effect,
• MeSH
• antikarcinogenní látky farmakologie   terapeutické užití   MeSH
• fytonutrienty farmakologie   terapeutické užití   MeSH
• karcinogeneze účinky léků   MeSH
• karcinogeny toxicita   MeSH
• lidé MeSH
• potraviny škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antikarcinogenní látky MeSH
• fytonutrienty MeSH
• karcinogeny MeSH

• MeSH
• adenokarcinom chemicky indukované   MeSH
• diethylstilbestrol škodlivé účinky   MeSH
• gestační stáří MeSH
• karcinogeny * MeSH
• kouření MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• maternofetální výměna látek účinky léků   MeSH
• nádory vaginy chemicky indukované   MeSH
• nádory chemicky indukované   MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• diethylstilbestrol MeSH
• karcinogeny * MeSH

Protein kinases represent a very pharmacologically attractive class of targets; however, some members of the family still remain rather unexplored. The biology and therapeutic potential of cdc-like kinases (CLKs) have been explored mainly over the last decade and the first CLK inhibitor, compound SM08502, entered clinical trials only recently. This review summarizes the biological roles and therapeutic potential of CLKs and their heretofore published small-molecule inhibitors, with a focus on the compounds' potential to be utilized as quality chemical biology probes.

• Klíčová slova
• CLK, MU1210, SGC-CLK-1, SM08502, T3, cdc-like kinase, chemical biology, chemical probe, inhibitor, tool compound,
• MeSH
• inhibitory proteinkinas farmakologie   terapeutické užití   MeSH
• karcinogeneze účinky léků   metabolismus   MeSH
• lidé MeSH
• protein-serin-threoninkinasy antagonisté a inhibitory   chemie   genetika   metabolismus   MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• tyrosinkinasy antagonisté a inhibitory   chemie   genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• Clk dual-specificity kinases MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• protein-serin-threoninkinasy MeSH
• protinádorové látky MeSH
• tyrosinkinasy MeSH

Tumor development is modulated by the interplay between the transformed cells and the host, and produces changes in the immune system. We followed the cancer progression and the variation of immune parameters in a rat in vivo model of induced colorectal carcinoma. Retrospective data collected from different experiments illustrated the dynamics of the tumor development, and of the immune cells (NK, NKT, T, CD4+, CTL, B and gammadeltaTCR+ cells), cytotoxicity, and CD4/CD8 ratio, at the third, sixth and eighth month of carcinogenesis. The chemically-induced carcinogenesis involved the complete large bowel, with progressive generation of multiple tumors during the complete considered period. Reduction in number and function of cytotoxic and regulatory cells of the innate immunity were crucial for cancer progression.

• MeSH
• buňky NK imunologie   MeSH
• cytotoxicita imunologická MeSH
• imunita MeSH
• kolorektální nádory etiologie   imunologie   patologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• poměr CD4 a CD8 lymfocytů MeSH
• potkani Wistar MeSH
• receptory antigenů T-buněk gama-delta analýza   MeSH
• T-lymfocyty - podskupiny imunologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptory antigenů T-buněk gama-delta MeSH

• Klíčová slova
• CARCINOGENS *, CELL DIVISION *, DNA, NEOPLASM *, EXPERIMENTAL LAB STUDY *, METABOLISM *, MUTATION *, ONCOGENIC VIRUSES *, RNA, NEOPLASM *, TOXICOLOGIC REPORT *,
• MeSH
• buněčné dělení * MeSH
• DNA nádorová * MeSH
• DNA * MeSH
• karcinogeneze * MeSH
• karcinogeny * MeSH
• metabolismus * MeSH
• mutace * MeSH
• nádory * MeSH
• nukleové kyseliny * MeSH
• onkogenní viry * MeSH
• RNA nádorová * MeSH
• RNA * MeSH
• toxikologie * MeSH
• výzkum * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA nádorová * MeSH
• DNA * MeSH
• karcinogeny * MeSH
• nukleové kyseliny * MeSH
• RNA nádorová * MeSH
• RNA * MeSH

Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.

• MeSH
• karcinogeneze chemicky indukované   MeSH
• lidé MeSH
• nádorové mikroprostředí účinky léků   MeSH
• nádory chemicky indukované   MeSH
• nebezpečné látky škodlivé účinky   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• nebezpečné látky MeSH