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Mutation Research Mar 2004The potential role of genotoxicity in human leukemias associated with benzene (BZ) exposures was investigated by a systematic review of over 1400 genotoxicity test... (Review)
Review
The potential role of genotoxicity in human leukemias associated with benzene (BZ) exposures was investigated by a systematic review of over 1400 genotoxicity test results for BZ and its metabolites. Studies of rodents exposed to radiolabeled BZ found a low level of radiolabel in isolated DNA with no preferential binding in target tissues of neoplasia. Adducts were not identified by 32P-postlabeling (equivalent to a covalent binding index <0.002) under the dosage conditions producing neoplasia in the rodent bioassays, and this method would have detected adducts at 1/10,000th the levels reported in the DNA-binding studies. Adducts were detected by 32P-postlabeling in vitro and following high acute BZ doses in vivo, but levels were about 100-fold less than those found by DNA binding. These findings suggest that DNA-adduct formation may not be a significant mechanism for BZ-induced neoplasia in rodents. The evaluation of other genotoxicity test results revealed that BZ and its metabolites did not produce reverse mutations in Salmonella typhimurium but were clastogenic and aneugenic, producing micronuclei, chromosomal aberrations, sister chromatid exchanges and DNA strand breaks. Rodent and human data were compared, and BZ genotoxicity results in both were similar for the available tests. Also, the biotransformation of BZ was qualitatively similar in rodents, humans and non-human primates, further indicating that rodent and human genotoxicity data were compatible. The genotoxicity test results for BZ and its metabolites were the most similar to those of topoisomerase II inhibitors and provided less support for proposed mechanisms involving DNA reactivity, mitotic spindle poisoning or oxidative DNA damage as genotoxic mechanisms; all of which have been demonstrated experimentally for BZ or its metabolites. Studies of the chromosomal translocations found in BZ-exposed persons and secondary human leukemias produced by topoisomerase II inhibitors provide some additional support for this mechanism being potentially operative in BZ-induced leukemia.
Topics: Animals; Benzene; Biological Assay; DNA Damage; Female; Humans; Male; Mutagenicity Tests; Mutagens; Topoisomerase II Inhibitors
PubMed: 15164977
DOI: 10.1016/s1383-5742(03)00053-x -
Environment International Feb 2011Several mechanisms are suspected to underlie adverse birth outcomes among mothers exposed to air pollutants, including inflammation, direct toxic effects on fetuses and... (Review)
Review
BACKGROUND
Several mechanisms are suspected to underlie adverse birth outcomes among mothers exposed to air pollutants, including inflammation, direct toxic effects on fetuses and the placenta, displacement of the oxygen-hemoglobin dissociation curve, and formation of DNA adducts.
OBJECTIVE
To systematically review the association between air pollutants and birth outcomes of low birth weight (LBW), preterm (PTB) and small for gestational age (SGA) births.
METHODS
Electronic databases and bibliographies of identified articles were searched for English language studies reporting on birth outcomes. Included studies were assessed for risks of bias in the selection, exposure assessment, confounder adjustment, analyses, outcomes assessment, and attrition. Unadjusted and adjusted estimates from included studies were extracted. Methodological differences between the studies were evaluated.
RESULTS
A total of 41 studies, mostly with a moderate risk of biases due to indirect assessment methods employed, met the eligibility criteria. Exposure to sulphur dioxide was associated with PTB, exposure to fine particulate matter (PM) of ≤2.5 μM was associated with LBW, PTB and SGA births, and exposure to coarse PM of ≤10 μM was associated with SGA births. The evidence for nitrous oxide, nitrogen dioxide, ozone and carbon monoxide was inconclusive.
CONCLUSIONS
Reported associations, and lack thereof, between individual air pollutants and birth outcomes have differed across published studies. This heterogeneity and/or absence of association may be due to difficulty in quantifying exposure, method of ascertainment, time of measurement and collinearity between pollutants. Important future research directions include developing improved methods to detect the duration and intensity of exposure, including entire populations, as well as performing well-designed nested studies that ascertain complete outcomes, avoiding residual confounding, and adjusting for residential mobility.
Topics: Air Pollutants; Air Pollution; Birth Weight; Female; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Inhalation Exposure; Male; Maternal Exposure; Particulate Matter; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Sulfur Dioxide
PubMed: 21112090
DOI: 10.1016/j.envint.2010.10.009 -
International Journal of Molecular... Nov 2022Aldehydes, particularly acetaldehyde, are carcinogenic molecules and their concentrations in foodstuffs should be controlled to avoid upper aerodigestive tract (UADT)... (Review)
Review
Aldehydes, particularly acetaldehyde, are carcinogenic molecules and their concentrations in foodstuffs should be controlled to avoid upper aerodigestive tract (UADT) and liver cancers. Highly reactive, acetaldehyde forms DNA and protein adducts, impairing physiological functions and leading to the development of pathological conditions. The consumption of aged beer, outside of the ethanol metabolism, exposes habitual drinkers to this carcinogen, whose concentrations can be over-increased due to post-brewing chemical and biochemical reactions. Storage-related changes are a challenge faced by the brewing industry, impacting volatile compound formation and triggering flavor instability. Aldehydes are among the volatile compounds formed during beer aging, recognized as off-flavor compounds. To track and understand aldehyde formation through multiple pathways during beer storage, consequent changes in flavor but particularly quality losses and harmful compound formation, this systematic review reunited data on volatile compound profiles through gas chromatography analyses from 2011 to 2021. Conditions to avoid flavor instability and successful methods for reducing beer staling, and consequent acetaldehyde accumulation, were raised by exploring the dynamic conversion between free and bound-state aldehydes. Future research should focus on implementing sensory analyses to investigate whether adding aldehyde-binding agents, e.g., cysteine and bisulfite, would contribute to consumer acceptance, restore beer flavor, and minimize acetaldehyde-related health damage.
Topics: Humans; Aged; Acetaldehyde; Aldehydes; Beer; Carcinogens; Carcinogenesis
PubMed: 36430619
DOI: 10.3390/ijms232214147 -
Chemosphere Mar 2022Breast cancer (BC) is the most frequently diagnosed cancer in women. However, only 58% of cases have been associated with known risk factors (reproductive, hormonal,... (Meta-Analysis)
Meta-Analysis
Breast cancer (BC) is the most frequently diagnosed cancer in women. However, only 58% of cases have been associated with known risk factors (reproductive, hormonal, lifestyles, and genetic), and the rest to unknown causes. Nevertheless, growing evidence suggests that exposure to environmental contaminants is an important risk factor for BC. Polycyclic aromatic hydrocarbons (PAHs) are formed during organic matter combustion, including smoking, grilled meat, and fuels, and are important carcinogenic constituents of environmental pollution. We examined the information generated by epidemiological studies evaluating the association between BC and PAHs exposure from multiple sources. Our work was conducted according to Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology (COSMOS-E) guidelines. We searched PubMed, Web of Science, and Scopus from January 2000 to December 2019. A total of 124 records were identified, and only 23 articles met all inclusion criteria. Occupational and/or environmental exposure to PAHs was significantly associated with BC, irrespective of exposure being assessed by direct or indirect methods. CYP1A1 and CYP1B1 adverse polymorphisms, familial BC history and smoking status, significantly strengthened the association between PAHs exposure and BC, whereas high fruit and vegetable intake had antagonistic associations. The positive relationships obtained in the studies here reviewed indicated that PAHs exposure is a risk factor for BC. Research needs include the improvement of exposure assessment, particularly identification of specific PAHs, reconstruction of time-varying and distant past exposures and further studies on the interaction between known BC factors and modifiable diet and life-style factors allowing BC prevention and control.
Topics: Breast Neoplasms; Carcinogens; Environmental Exposure; Environmental Pollution; Female; Humans; Polycyclic Aromatic Hydrocarbons
PubMed: 34929281
DOI: 10.1016/j.chemosphere.2021.133237 -
International Journal of Trichology 2022Smoking and its role in Androgenetic Alopecia has long been debated. Smoking may lead to hair loss by vasoconstriction, by forming DNA adducts, free radical damage to... (Review)
Review
Smoking and its role in Androgenetic Alopecia has long been debated. Smoking may lead to hair loss by vasoconstriction, by forming DNA adducts, free radical damage to hair follicle, by enhancing senescence and hormonal effects. We have reviewed the available literature on AGA and smoking. Data available show that there is a significant association between smoking and AGA. However, studies demonstrating the benefit of avoidance of smoking in improving hair loss are lacking. Furthermore, large controlled studies with histological documentation are still unavailable to affirm the findings.
PubMed: 35531482
DOI: 10.4103/ijt.ijt_59_21 -
Journal of Occupational and... Sep 2009Exposure monitoring programs have been used in the aluminum smelter industry for decades to decrease the risk of cancer from exposure to polycyclic aromatic hydrocarbons... (Review)
Review
Exposure monitoring programs have been used in the aluminum smelter industry for decades to decrease the risk of cancer from exposure to polycyclic aromatic hydrocarbons (PAHs). Biological monitoring of PAHs incorporates all routes of exposure. Measuring postshift urinary 1-hydroxypyrene (1OHP), a metabolite of pyrene, determines worker's daily PAH exposures, while measuring DNA adducts reflect chronic exposures to PAHs. We reviewed the scientific literature to identify changes over time in (1) 1OHP levels, (2) DNA adduct levels, and (3) other contributing factors associated with 1OHP and DNA adduct levels in the aluminum smelter industry. No trends were observed in 1OHP and DNA adduct levels. This could be due to variable selection of study populations and poorly identified job tasks that prevent comparison of jobs across plants and times, unassessed worker exposure variability, and the impact of cumulative exposures. Thus, it cannot be demonstrated that the use of biological monitoring to estimate PAH exposures has brought about an exposure reduction in the industry. Future studies should be aimed at follow-up in workplaces where dermal and inhalation exposure interventions have been employed. Inconsistent findings were also observed in the analysis of CYP1A1, GSTM1, and GSTP1 polymorphisms and their effect on biomarker levels.
Topics: Aluminum; Biomarkers; Carcinogens, Environmental; DNA Adducts; Female; Humans; Male; Metallurgy; Occupational Exposure; Polycyclic Aromatic Hydrocarbons; Pyrenes
PubMed: 19629825
DOI: 10.1080/15459620903094810 -
Occupational and Environmental Medicine Sep 2012The association between ambient air pollution exposure and lung cancer risk has been investigated in prospective studies and the results are generally consistent,... (Review)
Review
The association between ambient air pollution exposure and lung cancer risk has been investigated in prospective studies and the results are generally consistent, indicating that long-term exposure to air pollution may cause lung cancer. Despite the prospective nature and consistent findings of these studies, causality assessment can benefit from biomarker research. In the present systematic review, we assess the contribution of intermediate biomarkers in epidemiological studies, to ascertain whether their measurement reinforces causal reasoning. We have reviewed 524 papers which described the relationships between ambient air pollution and biological markers of dose and early response. The evidence for each marker was evaluated using assessment criteria which rate a group of studies from A (strong) to C (weak) on amount of evidence, replication of findings, and protection from bias. Biomarkers that scored A or B for all three criteria are included here. The markers that fulfilled the inclusion criteria are: 1-hydroxypyrene, DNA adducts, chromosomal aberrations, micronuclei, oxidative damage to nucleobases, and methylation changes. These biomarkers cover the whole spectrum of disease onset and progression from external exposure to tumour formation and some have also been suggested as risk predictors of future cancer, reinforcing causal reasoning. However, methodological issues such as confounding, publication bias and use of surrogate tissues instead of target tissues in studies on these markers are of concern. The identified biological markers have potential to shed light on the pathways of carcinogenesis, thus defining the association more clearly for public health interventions.
Topics: Air Pollution; Biomarkers; DNA Adducts; Environmental Exposure; Humans; Lung Neoplasms; Methylation; Micronuclei, Chromosome-Defective; Oxidative Stress; Pyrenes
PubMed: 22773658
DOI: 10.1136/oemed-2011-100566 -
Cancer Dec 2008The incidence of cancer during pregnancy is increasing given the trend for women to postpone childbearing. Knowledge of the potential toxicity and teratogenicity of... (Review)
Review
The incidence of cancer during pregnancy is increasing given the trend for women to postpone childbearing. Knowledge of the potential toxicity and teratogenicity of chemotherapy agents is crucial for patient counseling. Platinum derivatives are active against various malignancies that occur more frequently during pregnancy: melanoma, cervical and ovarian cancers, and lung cancer. The authors of this article performed a systematic review of reports documenting the use of platinum derivatives during pregnancy in the English literature from 1977 through January 2008. Forty-three pregnancies were described: 36 patients received cisplatin, 6 patients received carboplatin, and 1 patient received both drugs. Two fetal malformations occurred after in utero exposure to cisplatin, but the causative link between cisplatin administration and these malformations remains speculative. However, either detectable cisplatin levels or platinum-DNA adducts were observed in neonates who were exposed to platinum derivatives during the third trimester, providing evidence for a late-onset transplacental transfer of these drugs. The administration of platinum derivatives, although feasible during the second and third trimesters of pregnancy, raises concern regarding the transplacental transfer of these drugs in late pregnancy and has unknown short- and long-term effects.
Topics: Abnormalities, Drug-Induced; Antineoplastic Agents; Carboplatin; Cisplatin; Female; Humans; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Trimester, Third
PubMed: 18985677
DOI: 10.1002/cncr.23935 -
Environmental Health : a Global Access... Jul 2017Air pollution is involved in many pathologies. These pollutants act through several mechanisms that can affect numerous physiological functions, including reproduction:... (Review)
Review
BACKGROUND
Air pollution is involved in many pathologies. These pollutants act through several mechanisms that can affect numerous physiological functions, including reproduction: as endocrine disruptors or reactive oxygen species inducers, and through the formation of DNA adducts and/or epigenetic modifications. We conducted a systematic review of the published literature on the impact of air pollution on reproductive function. Eligible studies were selected from an electronic literature search from the PUBMED database from January 2000 to February 2016 and associated references in published studies. Search terms included (1) ovary or follicle or oocyte or testis or testicular or sperm or spermatozoa or fertility or infertility and (2) air quality or O or NO or PM2.5 or diesel or SO or traffic or PM10 or air pollution or air pollutants. The literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We have included the human and animal studies corresponding to the search terms and published in English. We have excluded articles whose results did not concern fertility or gamete function and those focused on cancer or allergy. We have also excluded genetic, auto-immune or iatrogenic causes of reduced reproduction function from our analysis. Finally, we have excluded animal data that does not concern mammals and studies based on results from in vitro culture. Data have been grouped according to the studied pollutants in order to synthetize their impact on fertility and the molecular pathways involved.
CONCLUSION
Both animal and human epidemiological studies support the idea that air pollutants cause defects during gametogenesis leading to a drop in reproductive capacities in exposed populations. Air quality has an impact on overall health as well as on the reproductive function, so increased awareness of environmental protection issues is needed among the general public and the authorities.
Topics: Air Pollutants; Air Pollution; Animals; Female; Gametogenesis; Humans; Infertility; Male; Mammals
PubMed: 28754128
DOI: 10.1186/s12940-017-0291-8 -
Evidence Report/technology Assessment Nov 2010The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the... (Review)
Review
OBJECTIVES
The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the risk of developing breast and colorectal cancers.
DATA SOURCES
We searched 11 external databases, including PubMed® and Embase, for studies on possible mechanisms. These searches used Medical Subject Headings and free text words to identify relevant evidence.
REVIEW METHODS
Two reviewers independently screened search results, selected studies to be included, and reviewed each trial for inclusion. We manually examined the bibliographies of included studies, scanned the content of new issues of selected journals, and reviewed relevant gray literature for potential additional articles.
RESULTS
Breast Cancer. Five human and 15 animal studies identified in our searches point to a connection between alcohol intake and changes in important metabolic pathways that when altered may increase the risk of developing breast cancer. Alterations in blood hormone levels, especially elevated estrogen-related hormones, have been reported in humans. Several cell line studies suggest that the estrogen receptor pathways may be altered by ethanol. Increased estrogen levels may increase the risk of breast cancer through increases in cell proliferation and alterations in estrogen receptors. Human studies have also suggested a connection with prolactin and with biomarkers of oxidative stress. Of 15 animal studies, six reported increased mammary tumorigenesis (four administered a co-carcinogen and two did not). Other animal studies reported conversion of ethanol to acetaldehyde in mammary tissue as having a significant effect on the progression of tumor development. Fifteen cell line studies suggested the following mechanisms: Increased hormonal receptor levels. Increased cell proliferation. A direct stimulatory effect. DNA adduct formation. Increase cyclic adenosine monophosphate (camp). Change in potassium channels. Modulation of gene expression. Colorectal Cancer. One human tissue study, 19 animal studies (of which 12 administered a co-carcinogen and seven did not), and 10 cell line studies indicate that ethanol and acetaldehyde may alter metabolic pathways and cell structures that increase the risk of developing colon cancer. Exposure of human colonic biopsies to acetaldehyde suggests that acetaldehyde disrupts epithelial tight junctions. Among 19 animal studies the mechanisms considered included: Mucosal damage after ethanol consumption. Increased degradation of folate. Stimulation of rectal carcinogenesis. Increased cell proliferation. Increased effect of carcinogens. Ten cell line studies suggested: Folate uptake modulation. Tumor necrosis factor modulation. Inflammation and cell death. DNA adduct formation. Cell differentiation. Modulation of gene expression. One study used a combination of animal and cell line and suggested intestinal cell proliferation and disruption of cellular signals as possible mechanisms.
CONCLUSIONS
Based on our systematic review of the literature, many potential mechanisms by which alcohol may influence the development of breast or colorectal cancers have been explored but the exact connection or connections remain unclear. The evidence points in several directions but the importance of any one mechanism is not apparent at this time.
Topics: Alcohol Drinking; Animals; Breast Neoplasms; Cell Proliferation; Colorectal Neoplasms; Estrogens; Ethanol; Female; Humans; Male; Mammary Neoplasms, Animal; Oxidative Stress; Prolactin; Receptors, Estrogen; Risk
PubMed: 23126574
DOI: No ID Found