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1.
Chemosphere ; 357: 141786, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38537716

ABSTRACT

Arsenic (As) contaminated water, especially groundwater reservoirs, is a major issue worldwide owing to its hazardous consequences on human health and the global environment issues. Also, irrigating agricultural fields with As-contaminated water not only produces an accumulation of As in the soil but also compromises food safety due to As entering into agricultural products. Hence, there is an urgent need to develop an efficient method for As removal in water. Fe-based MOFs have attained special attention due to their low toxicity, high water stability, better physical and chemical properties, and high abundance of iron. The arsenic species removal by Fe-MOF follows the adsorption and oxidation mechanism where As (III) converts into As (V). Moreover, the adsorption mechanism is facilitated by electrostatic interactions, H-bonding, acid-base interaction, hydrophobic interactions, van der Waals forces, π-π stacking interactions, and coordinative bindings responsible for Fe-O-As bond generation. This review thoroughly recapitulates and analyses recent advancements in the facile synthesis and potential application of Fe-based MOF adsorbents for the elimination of As ions. The most commonly employed hydro/solvothermal, ultrasonic, microwave-assisted, mechanochemical, and electrochemical synthesis for Fe-MOF has been discussed along with their adsorptive and oxidative mechanisms involved in arsenic removal. The effects of factors like pH and coexisting ions have also been discussed. Lastly, the article also proposed the prospects for developing the application of Fe-based MOF in treating As-contaminated water.


Subject(s)
Arsenic , Iron , Metal-Organic Frameworks , Water Pollutants, Chemical , Water Purification , Arsenic/chemistry , Arsenic/analysis , Adsorption , Water Pollutants, Chemical/chemistry , Iron/chemistry , Water Purification/methods , Metal-Organic Frameworks/chemistry , Catalysis , Oxidation-Reduction , Groundwater/chemistry
2.
Bioorg Med Chem ; 23(21): 6891-9, 2015 Nov 01.
Article in English | MEDLINE | ID: mdl-26474663

ABSTRACT

Potent, selective antitumour AhR ligands 5F 203 and GW 610 are bioactivated by CYPs 1A1 and 2W1. Herein we reason that DNA adducts' generation resulting in lethal DNA double strand breaks (DSBs) underlies benzothiazoles' activity. Treatment of sensitive carcinoma cell lines with GW 610 generated co-eluting DNA adducts (R(2)>0.7). Time-dependent appearance of γ-H2AX foci revealed subsequent DNA double strand breaks. Propensity for systemic toxicity of benzothiazoles steered development of prodrugs' hydrogels for localised delivery. Clinical applications of targeted therapies include prevention or treatment of recurrent disease after surgical resection of solid tumours. In vitro evaluation of 5F 203 prodrugs' activity demonstrated nanomolar potency against MCF-7 breast and IGROV-1 ovarian carcinoma cell lines.


Subject(s)
Antineoplastic Agents/chemical synthesis , DNA Adducts/analysis , Hydrogels/chemistry , Prodrugs/chemical synthesis , Thiazoles/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Benzothiazoles/chemical synthesis , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A1/metabolism , DNA Adducts/metabolism , Drug Resistance, Neoplasm , Gene Expression Regulation/drug effects , Histones/metabolism , Humans , Microscopy, Confocal , Prodrugs/chemistry , Prodrugs/pharmacology , Resveratrol , Stilbenes/chemistry , Thiazoles/chemical synthesis , Thiazoles/pharmacology
4.
Cochrane Database Syst Rev ; (10): CD008066, 2011 Oct 05.
Article in English | MEDLINE | ID: mdl-21975777

ABSTRACT

BACKGROUND: Obesity is a global public health threat. The transtheoretical model stages of change (TTM SOC) model has long been considered a useful interventional approach in lifestyle modification programmes, but its effectiveness in producing sustainable weight loss in overweight and obese individuals has been found to vary considerably.  OBJECTIVES: To assess the effectiveness of dietary and physical activity interventions based on the transtheoretical model, to produce sustainable weight loss in overweight and obese adults. SEARCH STRATEGY: Studies were obtained from searches of multiple electronic bibliographic databases. Date of last search for The Cochrane Library was issue 10, 2010, for MEDLINE Dezember 2010, for EMBASE January 2011 and for PSYCHINFO Januar 2011. SELECTION CRITERIA: Trials were included if they fulfilled the following criteria: randomised controlled clinical trials using TTM SOC as a model, theoretical framework or guideline in designing lifestyle modification strategies, mainly dietary and physical exercise versus a comparison intervention of usual care; one of the outcome measures of the study was weight loss; and participants were overweight or obese adults. DATA COLLECTION AND ANALYSIS: Two researchers independently applied the inclusion criteria to the identified studies and assessed risk of bias. Disagreement was resolved by discussion or by intervention of a third party. Descriptive analysis was conducted for the review. MAIN RESULTS: A total of five studies met the inclusion criteria and a total of 3910 participants were evaluated. The total number of participants randomised to intervention groups was 1834 and 2076 were randomised to control groups. Overall risk of bias was high. The trials varied in length of intervention from six weeks to 24 months, with a  median length of nine months. The intervention was found to have limited impact on weight loss (about 2 kg or less) and other outcome measures. There was no conclusive evidence for sustainable weight loss. However, TTM SOC and a combination of physical activity, diet and other interventions tended to produce significant outcomes (particularly change in physical activity and dietary intake). TTM SOC was used inconsistently as a theoretical framework for intervention in the trials. Death and weight gain are the two adverse events reported by the included trials. None of the trials reported health-related quality of life, morbidity, and costs as outcomes. AUTHORS' CONCLUSIONS: TTM SOC and a combination of physical activity, diet and other interventions resulted in minimal weight loss, and there was no conclusive evidence for sustainable weight loss. The impact of TTM SOC as theoretical framework in weight loss management may depend on how it is used as a framework for intervention and in combination with other strategies like diet and physical activities.


Subject(s)
Diet, Reducing , Exercise , Models, Psychological , Obesity/therapy , Weight Loss , Adult , Health Behavior , Humans , Obesity/psychology , Overweight/psychology , Overweight/therapy , Randomized Controlled Trials as Topic
6.
Indian J Crit Care Med ; 13(2): 92-3, 2009.
Article in English | MEDLINE | ID: mdl-19881190

ABSTRACT

There is a definitive risk of venous air embolism when the fluid infusion is complete and the drip set is still open in a glass bottle.We have devised a novel way of preventing the chances of air embolism when the fluid in the glass bottle finishes. It really gives a "U" turn to the chances of venous air embolism.

7.
J Chromatogr B Analyt Technol Biomed Life Sci ; 877(20-21): 1957-61, 2009 Jul 01.
Article in English | MEDLINE | ID: mdl-19501556

ABSTRACT

The formation of 5-methyl-2'-deoxycytidine (5-MedC) following methylation of the C-5 position of cytosine in genomic DNA provides an epigenetic mechanism for the regulation of gene expression and cellular differentiation. We describe the development of a method using HPLC-ultraviolet (UV) detection for the accurate determination of 5-MedC in DNA. Genomic DNA was obtained from HeLa cells and rat liver tissue using an optimised anion-exchange column DNA extraction procedure incorporating a ribonuclease incubation step to remove any potential interference from RNA. Following extraction the DNA samples were enzymatically hydrolysed to 2'-deoxynucleosides using a combination of an endo-exonuclease plus 5'-exonuclease together with a 3'-nucleotidase. The hydrolysed DNA samples (10 microg on column) were analysed using narrow-bore reverse phase HPLC-UV detection. The level of 5-MedC in the DNA samples was expressed as a percentage of the level of 2'-deoxycytidine (dC) determined from calibration lines constructed using authentic standards for 5-MedC and dC. The percentage 5-MedC level determined for commercially available calf thymus DNA was 6.26%, for HeLa cell DNA was 3.02% and for rat liver DNA was 3.55%.


Subject(s)
Chromatography, High Pressure Liquid/methods , DNA/analysis , Deoxycytidine/analogs & derivatives , Spectrophotometry, Ultraviolet/methods , Animals , Cattle , Cell Line, Tumor , Deoxycytidine/analysis , Genome , HeLa Cells , Humans , Male , Rats , Rats, Wistar
8.
Chem Res Toxicol ; 22(6): 1181-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19449825

ABSTRACT

Acetaldehyde is an ubiquitous genotoxic compound that has been classified as a possible carcinogen to humans. It can react with DNA to form primarily a Schiff base N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) adduct. An online column-switching valve liquid chromatography tandem mass spectrometry (LC-MS/MS) selected reaction monitoring (SRM) method was developed for the determination of N(2)-ethylidene-dG adducts in DNA following reduction with sodium cyanoborohydride (NaBH(3)CN) to the chemically stable N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG) adduct. Accurate quantitation of the adduct was obtained by the addition of the [(15)N(5)]N(2)-ethyl-dG stable isotope-labeled internal standard prior to enzymatic hydrolysis of the DNA samples to 2'-deoxynucleosides with the incorporation of NaBH(3)CN in the DNA hydrolysis buffer. The method required 50 microg of hydrolyzed DNA on column for the analysis, and the limit of detection for N(2)-ethyl-dG was 2.0 fmol. The analysis of calf thymus DNA treated in vitro with acetaldehyde (ranging from 0.5 to 100 mM) or with the smoke generated from 1, 5, and 10 cannabis cigarettes showed linear dose-dependent increases in the level of N(2)-ethyl-dG adducts (r = 0.954 and r = 0.999, respectively). Similar levels (332.8 +/- 21.9 vs 348.4 +/- 19.1 adducts per 10(8) 2'-deoxynucleosides) of N(2)-ethyl-dG adducts were detected following the exposure of calf thymus DNA to 10 tobacco or 10 cannabis cigarettes. No significant difference was found in the levels of N(2)-ethyl-dG adducts in human lung DNA obtained from nonsmokers (n = 4) and smokers (n = 4) with the average level observed as 13.3 +/- 0.7 adducts per 10(8) 2'-deoxynucleosides. No N(2)-ethyl-dG adducts were detected in any of the DNA samples following analysis with the omission of NaBH(3)CN from the DNA hydrolysis buffer. In conclusion, these results provide evidence for the DNA damaging potential of cannabis smoke, implying that the consumption of cannabis cigarettes may be detrimental to human health with the possibility to initiate cancer development.


Subject(s)
Cannabis/chemistry , DNA Adducts/analysis , DNA Damage , Deoxyguanosine/analogs & derivatives , Marijuana Smoking , Acetaldehyde/chemistry , Acetaldehyde/toxicity , Adult , Carcinogens/chemistry , Chromatography, High Pressure Liquid , DNA/chemistry , DNA Adducts/chemistry , Deoxyguanosine/chemistry , Deoxyguanosine/metabolism , Humans , Lung/chemistry , Male , Middle Aged , Spectrometry, Mass, Electrospray Ionization
9.
Cochrane Database Syst Rev ; (1): CD000993, 2009 Jan 21.
Article in English | MEDLINE | ID: mdl-19160185

ABSTRACT

BACKGROUND: Vitamin C is one of the key antioxidant vitamins which is abundant in the extracellular fluid lining the lung and low vitamin C intake has been associated with pulmonary dysfunction. OBJECTIVES: To evaluate the evidence for the efficacy of vitamin C in the treatment of asthma. SEARCH STRATEGY: The Cochrane Airways Review Group asthma register was searched and bibliographies of studies identified were also checked for further trials. This review has been updated by searches to August 2008. SELECTION CRITERIA: Only randomised controlled trials were eligible for inclusion. Studies were considered for inclusion if they dealt with the treatment of asthma using vitamin C supplementation. Two independent reviewers identified potentially relevant studies using pre-defined criteria and selected studies for inclusion. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers. Information on patients, methods, interventions, outcomes and results was extracted using standard forms. MAIN RESULTS: Nine studies met the review entry criteria, randomising a total of 330 participants. Study design varied and the reporting was generally poor. Five trials contributed numerical data to the review. They provided outcome data on lung function, symptom scores, IgE levels and inhaled steroid use. One small study showed a significant difference in % drop in FEV1 post-exercise. AUTHORS' CONCLUSIONS: At present, evidence from randomised-controlled trials is insufficient to recommend a specific role for vitamin C in the treatment of asthma. Further methodologically strong and large-scale randomised controlled trials are needed in order to address the question of the effectiveness of vitamin C in children with asthma.


Subject(s)
Antioxidants/therapeutic use , Ascorbic Acid/therapeutic use , Asthma/drug therapy , Dietary Supplements , Humans , Randomized Controlled Trials as Topic
10.
Rapid Commun Mass Spectrom ; 23(1): 151-60, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19065576

ABSTRACT

Sensitive and reliable methods are required for the assessment of oxidative DNA damage, which can result from reactive oxygen species that are generated endogenously from cellular metabolism and inflammatory responses, or by exposure to exogenous agents. The development of a liquid chromatography/tandem mass spectrometry (LC/MS/MS) selected reaction monitoring (SRM) method is described, that utilises online column-switching valve technology for the simultaneous determination of two DNA adduct biomarkers of oxidative stress, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxodA). To allow for the accurate quantitation of both adducts the corresponding [(15)N(5)]-labelled stable isotope internal standards were synthesised and added prior to enzymatic hydrolysis of the DNA samples to 2'-deoxynucleosides. The method required between 10 and 40 microg of hydrolysed DNA on-column for the analysis and the limit of detection for both 8-oxodG and 8-oxodA was 5 fmol. The analysis of calf thymus DNA treated in vitro with methylene blue (ranging from 5 to 200 microM) plus light showed a dose-dependent increase in the levels of both 8-oxodG and 8-oxodA. The level of 8-oxodG was on average 29.4-fold higher than that of 8-oxodA and an excellent linear correlation (r = 0.999) was observed between the two adducts. The influence of different DNA extraction procedures for 8-oxodG and 8-oxodA levels was assessed in DNA extracted from rat livers following dosing with carbon tetrachloride. The levels of 8-oxodG and 8-oxodA were on average 2.9 (p = 0.018) and 1.4 (p = 0.018) times higher, respectively, in DNA samples extracted using an anion-exchange column procedure than in samples extracted using a chaotropic procedure, implying artefactual generation of the two adducts. In conclusion, the online column-switching LC/MS/MS SRM method provides the advantages of increased sample throughput with reduced matrix effects and concomitant ionisation suppression, making the method ideally suited when used in conjunction with chaotropic DNA extraction for the determination of oxidative DNA damage.


Subject(s)
Chromatography, High Pressure Liquid/methods , DNA/chemistry , Deoxyadenosines/analysis , Deoxyguanosine/analogs & derivatives , Tandem Mass Spectrometry/methods , 8-Hydroxy-2'-Deoxyguanosine , Animals , Calibration , Carbon Tetrachloride/chemistry , Cattle , Chromatography, High Pressure Liquid/instrumentation , Deoxyguanosine/analysis , Liver/chemistry , Male , Methylene Blue/chemistry , Rats , Rats, Wistar , Tandem Mass Spectrometry/instrumentation , Thymus Gland/chemistry
11.
Nucleic Acids Res ; 35(15): 5014-27, 2007.
Article in English | MEDLINE | ID: mdl-17636312

ABSTRACT

In this study, we investigated the products formed following the reaction of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (B[a]PDE) with 2'-deoxynucleoside 3'-monophosphates. The B[a]PDE plus 2'-deoxynucleotide reaction mixtures were purified using solid phase extraction (SPE) and subjected to HPLC with fluorescence detection. Fractions corresponding to reaction product peaks were collected and desalted using SPE prior to analysis for the presence of molecular ions corresponding to m/z 648, 632, 608 and 623 [M-H]- consistent with B[a]PDE adducted (either on the base or phosphate group) 2'-deoxynucleotides of guanine, adenine, cytosine and thymine, respectively, using LC-ESI-MS/MS collision-induced dissociation (CID). Reaction products were identified having CID product ion spectra containing product ions at m/z 452, 436 and 412 [(B[a]Ptriol+base)-H]-, resulting from cleavage of the glycosidic bond between the 2'-deoxyribose and base, corresponding to B[a]PDE adducts of guanine, adenine and cytosine, respectively. Further reaction products were identified having unique CID product ion spectra characteristic of B[a]PDE adduct formation with the phosphate group of the 2'-deoxynucleotide. The presence of product ions at m/z 399 and 497 were observed for all four 2'-deoxynucleotides, corresponding to [(B[a]Ptriol+phosphate)-H]- and [(2'-deoxyribose+phosphate+B[a]Ptriol)-H]-, respectively. In conclusion, this investigation provides the first direct evidence for the formation of phosphodiester adducts by B[a]PDE following reaction with 2'-deoxynucleotides.


Subject(s)
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/chemistry , Carcinogens/chemistry , DNA Adducts/chemistry , Deoxyribonucleotides/chemistry , 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/analysis , 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/isolation & purification , Chromatography, High Pressure Liquid , DNA Adducts/analysis , DNA Adducts/isolation & purification , Fluorescence , Phosphates/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry
12.
Mutat Res ; 620(1-2): 71-82, 2007 Jul 01.
Article in English | MEDLINE | ID: mdl-17434188

ABSTRACT

Epidemiological studies conducted in metropolitan areas have demonstrated that exposure to environmental air pollution is associated with increases in mortality. Carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) are the major source of genotoxic activities of organic mixtures associated with respirable particulate matter, which is a constituent of environmental air pollution. In this study,we wanted to evaluate the relationship between exposure to these genotoxic compounds present in the air and endogenous oxidative DNA damage in three different human populations exposed to varying levels of environmental air pollution. As measures of oxidative DNA damage we have determined 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and cyclic pyrimidopurinone N-1,N(2) malondialdehyde-2'-deoxyguanosine (M(1)dG) by the immunoslot blot assay from lymphocyte DNA of participating individuals. The level of endogenous oxidative DNA damage was significantly increased in individuals exposed to environmental air pollution compared to unexposed individuals from Kosice (8-oxodG adducts) and Sofia (M(1)dG adducts). However, there was no significant difference in the level of endogenous oxidative DNA and exposure to environmental air pollution in individuals from Prague (8-oxodG and M(1)dG adducts) and Kosice (M(1)dG adducts). The average level of M(1)dG adducts was significantly lower in unexposed and exposed individuals from Kosice compared to those from Prague and Sofia. The average level of 8-oxodG adducts was significantly higher in unexposed and exposed individuals from Kosice compared to those from Prague. A significant increasing trend according to the interaction of c-PAHs exposure and smoking status was observed in levels of 8-oxodG adducts in individuals from Kosice. However, no other relationship was observed for M(1)dG and 8-oxodG adduct levels with regard to the smoking status and c-PAH exposure status of the individuals. The conclusion that can be made from this study is that environmental air pollution may alter the endogenous oxidative DNA damage levels in humans but the effect appears to be related to the country where the individuals reside. Genetic polymorphisms of the genes involved in metabolism and detoxification and also differences in the DNA repair capacity and antioxidant status of the individuals could be possible explanations for the variation observed in the level of endogenous oxidative DNA damage for the different populations.


Subject(s)
Air Pollutants/toxicity , Carcinogens, Environmental/toxicity , DNA Damage , Polycyclic Aromatic Hydrocarbons/toxicity , 8-Hydroxy-2'-Deoxyguanosine , Chromatography, High Pressure Liquid , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Humans , Male , Mass Spectrometry , Occupational Exposure , Oxidation-Reduction , Police , Smoking
13.
Chem Res Toxicol ; 19(6): 868-78, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16780367

ABSTRACT

The polycyclic aromatic hydrocarbon, benzo[a]pyrene (B[a]P) is a proven animal carcinogen that is potentially carcinogenic to humans. B[a]P is an ubiquitous environmental pollutant and is also present in tobacco smoke, coal tar, automobile exhaust emissions, and charred food. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using electrospray ionization and selected reaction monitoring (SRM) has been developed for the detection of 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE-N(2)dG) adducts formed in DNA following the metabolic activation of B[a]P to benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (B[a]PDE). The method involves enzymatic digestion of the DNA sample to 2'-deoxynucleosides following the addition of a stable isotope internal standard, [(15)N(5)]B[a]PDE-N(2)dG, and then solid phase extraction to remove unmodified 2'-deoxynucleosides prior to analysis by LC-MS/MS SRM. The limit of detection of the method was 10 fmol (approximately 3 B[a]PDE-N(2)dG adducts per 10(8) 2'-deoxynucleosides) using 100 microg of calf thymus DNA as the matrix. Calf thymus DNA reacted with B[a]PDE in vitro and mouse liver DNA samples at different time points following dosing intraperitoneally with 50, 100, and 200 mg/kg B[a]P was analyzed. Three stereoisomers of the B[a]PDE-N(2)dG adduct were detected following the reaction of calf thymus DNA with B[a]PDE in vitro. The levels of B[a]PDE-N(2)dG DNA adducts in the mice livers were found to increase in a dose-dependent manner with adducts reaching maximal levels at 1-3 days and then gradually decreasing over time but still detectable after 28 days. A very good correlation (r = 0.962, p < 0.001) was observed between the results obtained for the mouse liver DNA samples using LC-MS/MS SRM as compared to those obtained using a (32)P-postlabeling method. However, the levels of adducts observed following (32)P-postlabeling using butanol enrichment were approximately 3.7-fold lower. The LC-MS/MS method allowed the more precise quantitation of DNA adduct levels that were structurally characterized, in addition to a reduction in the time taken to perform the analysis when compared with the (32)P-postlabeling method.


Subject(s)
Benzo(a)pyrene/chemistry , DNA Adducts/chemistry , DNA Adducts/genetics , Liver/chemistry , Liver/metabolism , Animals , Cattle , DNA/chemistry , Deoxyguanosine/chemistry , Gas Chromatography-Mass Spectrometry , Male , Mice , Molecular Structure , Phosphorus Radioisotopes
14.
Chem Biol Interact ; 153-154: 97-102, 2005 May 30.
Article in English | MEDLINE | ID: mdl-15935804

ABSTRACT

S-Phenylmercapturic acid (S-PMA), is a urinary metabolite of benzene, thought to be derived from the condensation product of benzene oxide with glutathione. S-PMA may be determined by GC, HPLC (UV or fluorescence detection), GC-MS, LC-MS/MS or immunoassays. The limit of sensitivities of most of these techniques is 1 microg/l urine or below. It has been suggested that S-PMA may have value as a biomarker for low level human exposure to benzene, in view of the facts that urinary excretion of S-PMA has been found to be related to airborne benzene in occupationally exposed workers, and that only low background levels of S-PMA have been found in control subjects. We have evaluated the use of S-PMA as a biomarker, using a commercially available analytical service, in a multicentre European study of populations exposed to varying levels of benzene, in Italy (Milan, Genoa) and in Bulgaria (Sofia). These were filling station attendants, urban policemen, bus drivers, petrochemical workers and referents (a total of 623 subjects). S-PMA was measured at the end of the work shift by an immunoassay procedure. Urinary benzene (in Milan only) and the benzene metabolite trans,trans-muconic acid (t,t-MA) were measured before and after the work shift. Air-borne benzene was measured as a monitor of exposure. Urinary benzene was the most discriminatory biomarker and showed a relationship with airborne benzene at all levels of exposure studied (including groups exposed to <0.1 ppm benzene), whereas t,t-MA and S-PMA, as determined by immunoassay, were suitable only in the highest exposed workers (petrochemical industry, geometric mean 1765 microg/m3 (0.55 ppm) benzene). All three biomarkers were positively correlated with smoking as measured by urinary cotinine).


Subject(s)
Acetylcysteine/analogs & derivatives , Air Pollutants, Occupational/analysis , Benzene/analysis , Environmental Monitoring/methods , Occupational Exposure , Acetylcysteine/urine , Air Pollutants, Occupational/urine , Biomarkers/urine , Bulgaria/epidemiology , Chromatography, High Pressure Liquid , Epidemiological Monitoring , Gas Chromatography-Mass Spectrometry , Gasoline , Humans , Immunoassay/methods , Italy/epidemiology , Sorbic Acid/analogs & derivatives , Sorbic Acid/analysis , Vehicle Emissions
15.
Chem Res Toxicol ; 18(2): 249-56, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15720129

ABSTRACT

Cigarette smoke contains a complex mixture of chemicals, including some that are genotoxic. A number of epidemiological and clinical studies have reported the association of increased DNA adduct levels with the development of lung cancer in smokers. The majority of chemicals present in cigarette smoke require cytochrome P450-mediated metabolic activation to form the ultimate reactive species that covalently binds with DNA. We have investigated the presence of a direct-acting ethylating agent present in cigarette smoke by studying the formation of N-7 ethylguanine (N-7EtG) following exposure of DNA to cigarette smoke in vitro. A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with multiple reaction monitoring (MRM) was developed for the detection of N-7EtG in DNA. DNA samples were subjected to thermal hydrolysis to selectively release the N-7EtG, which was then quantified by LC-MS/MS MRM using a stable isotope internal standard [15N5]N-7EtG. The limit of detection of the method for N-7EtG was 2.0 fmol injected on column with 100 microg of calf thymus DNA as the matrix (0.6 N-7EtG adducts per 10(8) nucleotides). A linear dose-response was observed for the formation of N-7EtG in calf thymus DNA treated with diethyl sulfate at concentrations ranging from 1 to 1000 microM. Calf thymus DNA treated with smoke generated from 1, 5, and 10 commercially available cigarettes resulted in the formation of 1.3, 3.6, and 8.4 N-7EtG adducts per 10(8) nucleotides, respectively. There was a positive correlation between the formation of N-7EtG and the number of cigarettes (r = 0.9938). These results confirm the presence of an as yet unidentified direct acting ethylating agent in cigarette smoke, which is present at levels that can produce DNA damage that could ultimately have adverse implications for human health, particularly in the case of the development of lung cancer.


Subject(s)
Alkylating Agents/chemistry , DNA Damage , Guanine/chemistry , Nicotiana/chemistry , Smoke , Animals , Cattle , Chromatography, Liquid/methods , DNA/chemistry , Guanine/analogs & derivatives , Humans , Spectrometry, Mass, Electrospray Ionization/methods
16.
Mutat Res ; 544(2-3): 397-402, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14644342

ABSTRACT

Exposure to high levels of environmental air pollution is known to be associated with an increased carcinogenic risk. The individual contribution to this risk derived from specific carcinogenic chemicals within the complex mixture of air pollution is less certain, but may be explored by the use of molecular epidemiological techniques. Measurements of biomarkers of exposure, of effect and of susceptibility provide information of potential benefit for epidemiological and cancer risk assessment. The application of such techniques has been mostly concerned in the past with the carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) that are associated with particulate matter in air pollution, and has showed clear evidence of genotoxic effects, such as DNA adducts, chromosome aberrations (CA) and ras oncogene overexpression, in environmentally exposed Czech and Polish populations. We are currently extending these studies by an investigation of populations exposed to environmental pollution in three European countries, Czech Republic, Slovak Republic and Bulgaria. This pays particular attention to PAHs, but also investigates the extent of radically induced (oxidative) DNA damage in the exposed populations. Policemen, bus drivers and controls, who carried personal monitors to determine their exposures to PAHs have been studied, and blood and urine were collected. Antioxidant and dietary status were assessed in these populations. Stationary monitors were also used for ambient air monitoring. Amongst the parameters studied in the biological samples were: (a) exposure biomarkers, such as PAH adducts with DNA, p53 and p21(WAF1) protein levels, (b) oxidative DNA damage, (c) the biological effect of the exposure by measurement of chromosome damage by fluorescence in situ hybridisation (FISH) or conventional methods, and (d) polymorphisms in carcinogen metabolising and DNA repair enzymes. Repair ability was also measured by the Comet assay. In vitro systems are being evaluated to characterise the genotoxicity of the organic compounds adsorbed to air particles.


Subject(s)
Carcinogens/toxicity , DNA Damage/drug effects , Environmental Pollutants/toxicity , Environmental Pollution , Polycyclic Aromatic Hydrocarbons/toxicity , Biomarkers , DNA Damage/genetics , Environmental Exposure , Environmental Monitoring/methods , Epidemiological Monitoring , Humans , Molecular Epidemiology/methods , Neoplasms/chemically induced , Neoplasms/epidemiology , Neoplasms/genetics , Neoplasms/prevention & control
17.
Am J Hum Biol ; 6(4): 425-436, 1994.
Article in English | MEDLINE | ID: mdl-28548255

ABSTRACT

Stature, weight, and emergence of deciduous and permanent teeth of 1,330 well-nourished girls from birth to 20 years belonging to well-off families residing in Delhi are reported. All subjects were measured on two occasions 1 year apart. In addition, each subject was examined for gingival emergence of deciduous or permanent teeth on both occasions. Data on age at menarche were also collected. Single-year velocities of stature and weight are highest during the first year. The peak of adolescent spurts in stature and weight velocities are observed at 11.0 and 12.0 years, respectively. The first deciduous tooth to emerge is the mandibular I1 , of girls at 7.6 months. The sequence of emergence based on ascending median ages is I1, I2, M1, C, and M2 for both maxillary as well as mandibular deciduous teeth. The permanent dentition starts with the emergence of mandibular M1 at 5.75 years. The sequence of emergence of permanent teeth is M1 , I1 , I2 , PM1 , C, PM2 , and M2 in the maxilla, and M1 , I1 , I2, C, PM1 , PM2 , and M2 in the mandible. Annual increase in number of permanent teeth erupted shows a spurt between 9 and 10 years of age. Median age at menarche is 12.37 ± 0.03 with a standard deviation of 0.8 years; it is about one and one-half years later than the estimated age at peak height velocity. Single-year velocities of stature and weight decline after the onset of menarche. An association of emergence of deciduous teeth with birth weight is observed. Newborns with higher birth weight tend to have more teeth emerged at one year of age compared to those having lower birth weight. In all age groups, girls who had experienced menarche are taller and heavier and have more erupted permanent teeth compared to those who have not yet attained menarche. Girls with earlier menarche apparently have short adult stature compared to those with later menarche. © 1994 Wiley-Liss, Inc.

18.
Am J Hum Biol ; 4(6): 757-766, 1992.
Article in English | MEDLINE | ID: mdl-28524631

ABSTRACT

The results of a cross-sectional anthropometric survey of 1,643 well-nourished girls, from birth to 20 years, from the city of Delhi (India) are reported. The standardized measurements of body weight, height/crown-heel length, sitting height/crown-rump length, biacromial and bicristal diameters, head circumference, chest girth, upper arm girth, calf girth and skinfolds at biceps, triceps, and subscapular regions were taken for each subject. Medians fall between the 10th and 25th percentiles of National Center for Health Statistics (NCHS) reference data for height and the 10th and 50th percentiles for weight. The mean height and weight of the present girls are above the national reference values given by Indian Council of Medical Research (ICMR). Means and standard deviations of the weight/height ratio and body mass index (BMI) are also presented. The height/weight ratio increases continuously with age to 18 years. The mean values of the BMI, however, decrease to 6 years, rising afterward to adulthood. Median ages of eruption of deciduous and permanent teeth are presented. The first deciduous tooth to emerge in present girls is mandibular I1 at 7.6 months. The sequence of emergence based on ascending median ages is I1 , I2 , M1 , C, and M2 for both maxillary as well as mandibular deciduous teeth. The permanent set of dentition starts with the emergence of mandibular M1 at 5.75 years. Despite the rapid physical growth of American and British girls, the present girls are ahead in dental emergence and show earlier emergence of maxillary and mandibular permanent premolars, suggesting a genetic basis for the emergence of deciduous and permanent teeth. Partial correlation coefficients with age constant between height and the number of erupted deciduous and permanent teeth are positive and significant, reflecting an association, to some degree, with height and weight. © 1992 Wiley-Liss, Inc.

19.
Indian J Dermatol Venereol Leprol ; 52(5): 272-274, 1986.
Article in English | MEDLINE | ID: mdl-28150614

ABSTRACT

Bacillemia was assessed in a single random blood sample of 30 untreated leprosy patients by employing direct blood smear method, haemolysis method, huffy coat method, and leucocyte adherence method.

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