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Strahlentherapie Und Onkologie : Organ... Sep 2022To evaluate the mutagen sensitivity phenotype on the risk of second primary cancer (SPC) in patients with head and neck squamous cell carcinoma (HNSCC), and to estimate...
PURPOSE
To evaluate the mutagen sensitivity phenotype on the risk of second primary cancer (SPC) in patients with head and neck squamous cell carcinoma (HNSCC), and to estimate the long-term rate of SPC and the outcome with SPC.
METHODS
A survey was made regarding SPC among 124 younger (≤ 50 years) adults with HNSCC who were enrolled in a pretreatment mutagen sensitivity investigation during 1996-2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantifying the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (> 1 b/c) or not hypersensitive (≤ 1 b/c).
RESULTS
Mean follow-up time for all patients was 68 months (range: 5-288 months), and the 15-year cancer-specific survival was 15%. Twenty patients (16%) developed a SPC (15-year estimated rate: 41%), and half of them was hypersensitive. The crude rate of SPC for hypersensitive (n = 65) or not hypersensitive (n = 59) patients were 15 and 17%, respectively (p = 0.4272). The 15-year estimated rate of SPC for hypersensitive and not hypersensitive patients was 36 and 48%, respectively (p = 0.3743). Gender, UICC stages, anatomical sites of index cancer did not prove to be a significant risk factor for SPC. Forty-five percent of SPC developed after the 10-year follow-up. The 3‑year cancer-specific survival was 23% with SPC.
CONCLUSION
According to our findings, mutagen hypersensitivity was not associated with an increased SPC risk in HNSCC patients. Patients are at a lifelong risk of developing a SPC. Survival with SPC is very poor.
Topics: Bleomycin; Carcinoma, Squamous Cell; Epithelial Cells; Head and Neck Neoplasms; Humans; Mutagens; Neoplasms, Second Primary; Squamous Cell Carcinoma of Head and Neck
PubMed: 35357513
DOI: 10.1007/s00066-022-01917-2 -
The American Journal of Clinical... Jun 2020Red and processed meat, recognized carcinogens, are risk factors for colorectal neoplasia, including polyps, the precursor for colorectal cancer. The mechanism is...
BACKGROUND
Red and processed meat, recognized carcinogens, are risk factors for colorectal neoplasia, including polyps, the precursor for colorectal cancer. The mechanism is unclear. One possible explanation is the mutagenic activity of these foods, perhaps due to generation during cooking [e.g., heterocyclic amine (HCA) intake]. Few studies have evaluated meat intake and sessile serrated lesion (SSL) risk, a recently recognized precursor, and no study has evaluated meat cooking methods and meat-derived mutagens with SSL risk.
OBJECTIVE
We evaluated intakes of meat, meat cooking methods, and inferred meat mutagens with SSL risk and in comparison to risk of other polyps.
METHODS
Meat, well-done meat, and inferred meat mutagen intakes were evaluated. Polytomous logistic regression models were used to estimate ORs and 95% CIs among cases (556 hyperplastic polyp, 1753 adenoma, and 208 SSL) and controls (3804) in the large colonoscopy-based, case-control study, the Tennessee Colorectal Polyp Study.
RESULTS
The highest quartile intakes of red meat (OR: 2.38; 95% CI: 1.44, 3.93), processed meat (OR: 2.03; 95% CI: 1.30, 3.17), well-done red meat (OR: 2.19; 95% CI: 1.34, 3.60), and the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQX; OR: 2.48; 95% CI: 1.49, 4.16) were associated with increased risk of SSLs in comparison to the lowest quartile intake.
CONCLUSIONS
High intakes of red and processed meats are strongly and especially associated with SSL risk and part of the association may be due to HCA intake. Future studies should evaluate other mechanism(s) and the potential for primary prevention.
Topics: Amines; Case-Control Studies; Colorectal Neoplasms; Cooking; Dietary Exposure; Female; Hot Temperature; Humans; Male; Meat; Middle Aged; Mutagens; Risk Factors; Tennessee
PubMed: 32077920
DOI: 10.1093/ajcn/nqaa030 -
Arhiv Za Higijenu Rada I Toksikologiju Sep 2016Knowing the mutagenic and carcinogenic properties of chemicals is very important for their hazard (and risk) assessment. One of the crucial events that trigger genotoxic... (Review)
Review
Knowing the mutagenic and carcinogenic properties of chemicals is very important for their hazard (and risk) assessment. One of the crucial events that trigger genotoxic and sometimes carcinogenic effects is the forming of adducts between chemical compounds and nucleic acids and histones. This review takes a look at the mechanisms related to specific functional groups (structural alerts or toxicophores) that may trigger genotoxic or epigenetic effects in the cells. We present up-to-date information about defined structural alerts with their mechanisms and the software based on this knowledge (QSAR models and classification schemes).
Topics: Carcinogens; Humans; Mutagens; Quantitative Structure-Activity Relationship; Risk Assessment
PubMed: 27749264
DOI: 10.1515/aiht-2016-67-2801 -
Toxicology Jun 2018Lower alkyl acrylate monomers include methyl-, ethyl-, n-butyl-, and 2-ethylhexyl acrylate. These acrylates are used in the manufacture of acrylic polymers and... (Review)
Review
Lower alkyl acrylate monomers include methyl-, ethyl-, n-butyl-, and 2-ethylhexyl acrylate. These acrylates are used in the manufacture of acrylic polymers and copolymers for plastics, food packaging, adhesives, and cosmetic formulations. Although there is limited potential for human environmental exposure, occupational exposure can occur via inhalation and dermal contact. Recently, new genotoxicity data have been generated, along with in silico and in vitro read-cross analyses, for these acrylates. The availability of high-throughput screening (HTS) data through the ToxCast™/Tox21 databases allows for consideration of computational toxicology and organization of these data according to the ten key characteristics of carcinogens. Therefore, we conducted a comprehensive review to evaluate the mechanistic, toxicokinetic, animal, and human data, including HTS data, for characterizing the potential carcinogenicity, mutagenicity, and genotoxicity of these acrylates. Toxicokinetic data demonstrate that these acrylates are metabolized rapidly by carboxylesterase hydrolysis and conjugation with glutathione. HTS data demonstrated an overall lack of bioactivity in cancer-related pathways. Overall, the genotoxicity and mutagenicity data support a cytotoxic, non-genotoxic mechanism for these acrylates. Cancer bioassay studies conducted by the oral, dermal, and inhalation routes in animal models with these acrylates did not show any increase in tumor incidence, with two exceptions. At high doses, and secondary to chronic site-of-contact irritation and corrosion, rodent forestomach tumors were induced by oral gavage dosing with ethyl acrylate, and skin tumors were observed following chronic dermal dosing with 2-ethylhexyl acrylate in C3H/HeJ inbred mice (a strain with deficiencies in wound healing), but not in the outbred NMRI strain. For both dermal and forestomach cancers, tumorigenesis is secondary to high doses and long-term tissue damage, shown to be reversible. With evidence that these chemicals are not genotoxic, and that they cause forestomach and dermal tumors through chronic irritation and regenerative proliferation mechanisms, these acrylates are unlikely to pose a human cancer hazard.
Topics: Acrylates; Animals; Carcinogenesis; Carcinogens; DNA Damage; Humans; Mutagens; Occupational Exposure; Signal Transduction
PubMed: 29689363
DOI: 10.1016/j.tox.2018.04.006 -
Journal of Applied Toxicology : JAT Apr 2010Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants... (Review)
Review
Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cII gene of rat liver and in the p53 and K-ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G : C --> T : A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs.
Topics: Animals; Carcinogens, Environmental; Chemical and Drug Induced Liver Injury; Chromosome Aberrations; DNA Damage; Humans; Mutagens; Mutation; Plants, Toxic; Pyrrolizidine Alkaloids
PubMed: 20112250
DOI: 10.1002/jat.1504 -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Methyl Methanesulfonate; Mutagenicity Tests; Mutagens; Neoplasms, Experimental
PubMed: 10476376
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Malondialdehyde; Mutagenicity Tests; Mutagens; Neoplasms, Experimental
PubMed: 10476374
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Topics: Aldehydes; Animals; Carcinogenicity Tests; Carcinogens; Epoxy Compounds; Humans; Mutagenicity Tests; Mutagens; Skin Neoplasms
PubMed: 10476428
DOI: No ID Found -
Food and Chemical Toxicology : An... Jan 20193-NOP (3-nitroxy-propanol) is a new development compound which reduces methane emission from ruminating animals. For registration purposes with emphasis on EU and North...
3-NOP (3-nitroxy-propanol) is a new development compound which reduces methane emission from ruminating animals. For registration purposes with emphasis on EU and North America data requirements, mutagenic and genotoxic potential was assessed following OECD protocols and respective guidance documents. 3-NOP mutagenicity and genotoxicity testing raised no flags with regard to these endpoints. In silico assessment of 3-NOP and its major plasma metabolite NOPA (3-nitroxy-propionic acid) were predicted negative with regard to the bacterial reverse mutation (Ames) test. Ames test, mouse lymphoma assay, in vitro micronucleus test, and the oral in vivo micronucleus test using rat bone marrow were all negative. Exposure of the rat bone marrow was verified by the presence of 3-NOP and its metabolites NOPA and HPA (3-hydroxy-propionic acid) a naturally occurring substance in mammals) in plasma following oral dosing. It is therefore concluded that 3-NOP and its metabolites pose no mutagenic and genotoxic potential.
Topics: 1-Propanol; Animals; Bacteria; Cell Line; DNA Damage; Mice; Micronucleus Tests; Mutagenicity Tests; Mutagens
PubMed: 30408540
DOI: 10.1016/j.fct.2018.11.010 -
Environment International Feb 2019The genotoxic, mutagenic and carcinogenic effects of polar polycyclic aromatic hydrocarbons (polar PAHs) are believed to surpass those of their parent PAHs; however,... (Review)
Review
The genotoxic, mutagenic and carcinogenic effects of polar polycyclic aromatic hydrocarbons (polar PAHs) are believed to surpass those of their parent PAHs; however, their environmental and human health implications have been largely unexplored. Oxygenated PAHs (oxy-PAHs) is a critical class of polar PAHs associated with carcinogenic effects without enzymatic activation. They also cause an upsurge in reactive oxygen species (ROS) in living cells. This results in oxidative stress and other consequences, such as abnormal gene expressions, altered protein activities, mutagenesis, and carcinogenesis. Similarly, some nitrated PAHs (N-PAHs) are probable human carcinogens as classified by the International Agency for Research on Cancer (IARC). Heterocyclic PAHs (polar PAHs containing nitrogen, sulphur and oxygen atoms within the aromatic rings) have been shown to be potent endocrine disruptors, primarily through their estrogenic activities. Despite the high toxicity and enhanced environmental mobility of many polar PAHs, they have attracted only a little attention in risk assessment of contaminated sites. This may lead to underestimation of potential risks, and remediation end points. In this review, the toxicity of polar PAHs and their associated mechanisms of action, including their role in mutagenic, carcinogenic, developmental and teratogenic effects are critically discussed. This review suggests that polar PAHs could have serious toxicological effects on human health and should be considered during risk assessment of PAH-contaminated sites. The implications of not doing so were argued and critical knowledge gaps and future research requirements discussed.
Topics: Biodegradation, Environmental; Biological Availability; Carcinogenesis; Carcinogens; DNA Damage; Environmental Health; Humans; Mutagens; Oxidative Stress; Polycyclic Aromatic Hydrocarbons
PubMed: 30622079
DOI: 10.1016/j.envint.2018.12.051