Prenatal exposure to particulate matter and ozone: Bulky DNA adducts, plasma isoprostanes, allele risk variants, and neonate susceptibility in the Mexico City Metropolitan Area.

Mexico City's Metropolitan Area (MCMA) includes Mexico City and 60 municipalities of the neighbor states. Inhabitants are exposed to emissions from over five million vehicles and stationary sources of air pollutants such as particulate matter (PM) and ozone. MCMA PM contains elemental carbon and organic carbon (OC). OCs include polycyclic aromatic hydrocarbons (PAHs), many of which induce mutagenic and carcinogenic DNA adducts. Gestational exposure to air pollution has been associated with increased risk of intrauterine growth restriction, preterm birth or low birth weight risk, and PAH-DNA adducts. These effects also depend on the presence of risk alleles. We investigated the presence of bulky PAH-DNA adducts, plasma 8-iso-PGF2α (8-iso-prostaglandin F2α ) and risk allele variants in neonates cord blood and their non-smoking mothers' leucocytes from families that were living in a highly polluted area during 2014-2015. The presence of adducts was significantly associated with both PM2.5 and PM10 levels, mainly during the last trimester of gestation in both neonates and mothers, while the last month of pregnancy was significant for the association between ozone levels and maternal plasma 8-iso-PGF2α . Fetal CYP1B1*3 risk allele was associated with increased adduct levels in neonates while the presence of the maternal allele significantly reduced the levels of fetal adducts. Maternal NQO1*2 was associated with lower maternal levels of adducts. Our findings suggest the need to reduce actual PM limits in MCMA. We did not observe a clear association between PM and/or adduct levels and neonate weight, length, body mass index, Apgar or Capurro score. Environ. Mol. Mutagen. 60:428-442, 2019. © 2019 Wiley Periodicals, Inc.

Seasonal variations in the levels of PAH-DNA adducts in young adults living in Mexico City.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous components of polluted air. The Mexico City Metropolitan Area (MCMA), one of the most densely populated areas in the world, is 2240 m above sea level. At this altitude, less oxygen is available, making combustion less efficient and therefore producing more PAH pollutants. According to the Automatic Monitoring Network in Mexico City (RAMA, for its Spanish initials; http://www.sma.df.gob.mx/simat2/informaciontecnica/index.php?opcion=5&opciondifusion_bd=90), which performs environmental monitoring, the critical air pollutants in Mexico City are ozone and particulate matter (PM). PM emissions increase during the dry season (winter to spring) and decrease during the rainy season (summer to autumn). The bioactivation of some PAHs produces reactive metabolites that bind to DNA, and the presence of elevated levels of PAH-DNA adducts in tissues such as blood lymphocytes represents an elevated risk for the development of cancer. We have compared the levels of PAH-DNA adducts and the percentage of cells with chromosomal aberrations (CWAs) using a matched set of peripheral blood lymphocytes obtained on two separate occasions from young non-smoking inhabitants of the MCMA (n = 92) during the 2006 dry season and the following rainy season. PAH-DNA adducts were analysed using the r7, t8-dihydroxy-t-9, 10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA chemiluminescence immunoassay (CIA). The percentages of CWA were determined in cultured lymphocytes from the same individuals. Both DNA adduct levels and chromosomal aberrations were tested for correlation with lifestyle and the polymorphisms of cytochromes P450 CYP1A1 and CYP1B1 as well as glutathione-S-transferases GSTM1 and GSTT1. The levels of PAH-DNA adducts were significantly higher (P < 0.001) in the dry season (10.66 ± 3.05 per 10(9) nt, n = 92) than during the rainy season (9.50 ± 2.85 per 10(9) nt, n = 92) and correlated with the seasonal levels of particulate matter with a diameter of ≤ 10 µm (PM(10)). The percentage of CWA was not seasonally related; however, significant associations between the number of risk alleles and adduct levels in the dry (R = 0.298, P = 0.048) and in the wet seasons (R = 0.473, P = 0.001) were observed.

Ultrasensitive simultaneous quantification of 1,N2-etheno-2'-deoxyguanosine and 1,N2-propano-2'-deoxyguanosine in DNA by an online liquid chromatography-electrospray tandem mass spectrometry assay.

Exocyclic DNA adducts produced by exogenous and endogenous compounds are emerging as potential tools to study a variety of human diseases and air pollution exposure. A highly sensitive method involving online reverse-phase high performance liquid chromatography with electrospray tandem mass spectrometry detection in the multiple reaction monitoring mode and employing stable isotope-labeled internal standards was developed for the simultaneous quantification of 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-epsilondGuo) and 1,N(2)-propano-2'-deoxyguanosine (1,N(2)-propanodGuo) in DNA. This methodology permits direct online quantification of 2'-deoxyguanosine and ca. 500 amol of adducts in 100 microg of hydrolyzed DNA in the same analysis. Using the newly developed technique, accurate determinations of 1,N(2)-etheno-2'-deoxyguanosine and 1,N(2)-propano-2'-deoxyguanosine levels in DNA extracts of human cultured cells (4.01 +/- 0.32 1,N(2)-epsilondGuo/10(8) dGuo and 3.43 +/- 0.33 1,N(2)-propanodGuo/10(8) dGuo) and rat tissue (liver, 2.47 +/- 0.61 1,N(2)-epsilondGuo/10(8) dGuo and 4.61 +/- 0.69 1,N(2)-propanodGuo/10(8) dGuo; brain, 2.96 +/- 1.43 1,N(2)-epsilondGuo/10(8) dGuo and 5.66 +/- 3.70 1,N(2)-propanodGuo/10(8) dGuo; and lung, 0.87 +/- 0.34 1,N(2)-epsilondGuo/10(8) dGuo and 2.25 +/- 1.72 1,N(2)-propanodGuo/10(8) dGuo) were performed. The method described herein can be used to study the biological significance of exocyclic DNA adducts through the quantification of different adducts in humans and experimental animals with pathological conditions and after air pollution exposure.

Mass spectrometric analysis of a cyclic 7,8-butanoguanine adduct of N-nitrosopyrrolidine: comparison to other N-nitrosopyrrolidine adducts in rat hepatic DNA.

The well established rat hepatocarcinogen N-nitrosopyrrolidine (NPYR, 1) requires metabolic activation to DNA adducts to express its carcinogenic activity. Among the NPYR-DNA adducts that have been identified, the cyclic 7,8-butanoguanine adduct 2-amino-6,7,8,9-tetrahydro-9-hydroxypyrido[2,1-f]purine-4(3H)-one (6) has been quantified using moderately sensitive methods, but its levels have never been compared to those of other DNA adducts of NPYR in rat hepatic DNA. Therefore, in this study, we developed a sensitive new LC-ESI-MS/MS-SRM method for the quantitation of adduct 6 and compared its levels to those of several other NPYR-DNA adducts formed by different mechanisms. The new method was shown to be accurate and precise, with good recoveries and low fmol detection limits. Rats were treated with NPYR by gavage at doses of 46, 92, or 184 mg/kg body weight and sacrificed 16 h later. Hepatic DNA was isolated and analyzed for NPYR-DNA adducts. Adduct 6 was by far the most prevalent, with levels ranging from about 900-3000 micromol/mol Gua and responsive to dose. Levels of adducts formed from crotonaldehyde, a metabolite of NPYR, were about 0.2-0.9 micromol/mol dGuo, while those of adducts resulting from reaction with DNA of tetrahydrofuranyl-like intermediates were in the range of 0.01-4 micromol/mol deoxyribonucleoside. The results of this study demonstrate that, among typical NPYR-DNA adducts, adduct 6 is easily the most abundant in hepatic DNA. Since previous studies have shown that it can be detected in the urine of NPYR-treated rats, the results suggest that it is a potential candidate as a biomarker for assessing human exposure to and metabolic activation of NPYR.

Exocyclic DNA adducts as biomarkers of lipid oxidation and predictors of disease. Challenges in developing sensitive and specific methods for clinical studies.

Exocyclic DNA adducts are emerging as potential new tools for the study of oxidative stress-related diseases as well as the determination of cancer etiology and cancer risk. It is important to determine whether levels of exocyclic DNA adducts reflect redox stress in vivo and what role these adducts play in human diseases. To answer these important questions, interindividual differences, tissue distribution, background levels, and repair have to be assessed. This review focuses on recent developments in the use of these adducts as possible biomarkers for disease risk related to oxidative stress and on the challenges in developing sensitive and specific methods for clinical studies.

Detection and quantification of 4-ABP adducts in DNA from bladder cancer patients.

We analyzed bladder DNA from 27 cancer patients for dG-C8-4-aminobiphenyl (dG-C8-ABP) adducts using the liquid chromatography tandem mass spectrometry method with a 700 attomol (1 adduct in 10(9) bases) detection limit. Hemoglobin (Hb) 4-aminobiphenyl (4-ABP) adduct levels were measured by gas chromatography-mass spectrometry. After isolation of dG-C8-ABP by immunoaffinity chromatography and further purification, deuterated (d9) dG-C8-ABP (MW=443 Da) was added to each sample. Structural evidence and adduct quantification were determined by selected reaction monitoring, based on the expected adduct ion [M+H+]+1, at m/z 435 with fragmentation to the product ion at m/z 319, and monitoring of the transition for the internal standard, m/z 444-->328. The method was validated by analysis of DNA (100 microg each) from calf thymus; livers from ABP-treated and untreated rats; human placentas; and TK6 lymphoblastoid cells. Adduct was detected at femtomol levels in DNA from livers of ABP-treated rats and calf thymus, but not in other controls. The method was applied to 41 DNA samples (200 microg each) from 27 human bladders; 28 from tumor and 14 from surrounding non-tumor tissue. Of 27 tissues analyzed, 44% (12) contained 5-80 dG-C8-ABP adducts per 10(9) bases; only 1 out of 27 (4%) contained adduct in both tumor and surrounding tissues. The Hb adduct was detected in samples from all patients, at levels of 12-1960 pg per gram Hb. There was no correlation between levels of DNA and Hb adducts. The presence of DNA adducts in 44% of the subjects and high levels of Hb adducts in these non-smokers indicate environmental sources of exposure to 4-ABP.

Biomarkers in maternal and newborn blood indicate heightened fetal susceptibility to procarcinogenic DNA damage.

Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) are widespread air contaminants released by transportation vehicles, power generation, and other combustion sources. Experimental evidence indicates that the developing fetus is more susceptible than the adult to carcinogenic effects of PAHs, although laboratory studies in rodents suggest that the dose to fetal tissues is an order of magnitude lower than that to maternal tissues. To assess fetal versus adult susceptibility to PAHs and environmental tobacco smoke (ETS), we compared carcinogen-DNA adducts (a biomarker associated with increased cancer risk) and cotinine (a biomarker of tobacco smoke exposure) in paired blood samples collected from mothers and newborns in New York City. We enrolled 265 nonsmoker African-American and Latina mother-newborn pairs in New York City between 1997 and 2001 (estimated average ambient air BaP concentrations < 0.5 ng/m3). Despite the estimated 10-fold lower fetal dose, mean levels of BaP-DNA adducts as determined by high-performance liquid chromatography-fluorescence were comparable in paired New York City newborn and maternal samples (0.24 adducts per 10(8) nucleotides, 45% of newborns with detectable adducts vs. 0.22 per 10(8) nucleotides, 41% of mothers with detectable adducts). However, by the Wilcoxon signed-rank test, the levels in newborns were higher (p = 0.02). Mean cotinine was higher in newborns than in mothers (1.7 ng/mL, 47% detectable vs. 1.28 ng/mL, 44% detectable). Consistent with our prior study in a Caucasian Polish population, these results indicate increased susceptibility of the fetus to DNA damage and reduced ability to clear ETS constituents. The findings have implications for risk assessment, given the need to protect children as a sensitive subset of the population.

Induction of 1,N(2)-etheno-2'-deoxyguanosine in DNA exposed to beta-carotene oxidation products.

Epidemiological studies testing the effect of beta-carotene in humans have found a relative risk for lung cancer in smokers supplemented with beta-carotene. We investigated the reactions of retinal and beta-apo-8'-carotenal, two beta-carotene oxidation products, with 2'-deoxyguanosine to evaluate their DNA damaging potential. A known mutagenic adduct, 1,N(2)-etheno-2'-deoxyguanosine, was isolated and characterized on the basis of its spectroscopic features. After treatment of calf thymus DNA with beta-carotene or beta-carotene oxidation products, significantly increased levels of 1,N(2)-etheno-2'-deoxyguanosine and 8-oxo-7,8-dihydro-2'-deoxyguanosine were quantified in DNA. These lesions are believed to be important in the development of human cancers. The results reported here may contribute toward an understanding of the biological effects of beta-carotene oxidation products.

Applications of capillary electrophoresis with laser-induced fluorescence for analysis of dGMP-BPDE adduct.

DNA adducts are thought to be crucial to the initiation of mutational and carcinogenic processes. Polycyclic aromatic hydrocarbons (PAHs) have been identified as one major source of carcinogenic risk since they can bind to DNA thus forming an adduct. Quantification of this adduct is important because it may correlate to the risk for cancer development. In this study, the adduct formed between 2'-deoxyguanosine 5'-monophosphate and benzo[ a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) was analyzed by capillary electrophoresis. Both capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MECC) modes with laser-induced fluorescence detection were used for the separation and analysis of DNA adducts. The exploration of capillary electrophoresis in several modes provided different separation mechanisms in which the stereochemical forms of the adduct could be separated. The best result obtained was using a coated fused-silica capillary in Tris-TAPS buffer, which provided high sensitivity with a detection limit of 2.5x10(-9) mol L(-1). MECC separation of the BPDE adduct, although less sensitive, provided an efficient enantioselective separation option.

Development of an on-line liquid chromatography-electrospray tandem mass spectrometry assay to quantitatively determine 1,N(2)-etheno-2'-deoxyguanosine in DNA.

A method involving on-line reversed-phase high-performance liquid chromatography with electrospray tandem mass spectrometry detection has been developed for the analysis of 1,N(2)-etheno-2'-deoxyguanosine in DNA. This methodology permits direct quantification of 20 fmol (7.4 adducts/10(8) dGuo) of the etheno adduct from approximately 350 microg of crude DNA hydrolysate. Using the newly developed technique, basal levels of 1,N(2)-etheno-2'-deoxyguanosine were determined in commercial calf thymus DNA (1.70 +/- 0.09 adducts/10(7) dGuo), in cultured mammalian cells (CV1-P) DNA (4.5 +/- 0.4 adducts/10(7) dGuo), and in untreated female rat liver DNA (5.22 +/- 1.37 adduct/10(7) dGuo). The mutagenicity of 1,N(2)-etheno-2'-deoxyguanosine had already been demonstrated by in vitro and in vivo systems. The method described here provides the first evidence of the occurrence of 1,N(2)-etheno-2'-deoxyguanosine as a basal endogenous lesion and may be usefully employed to assess the biological consequences of etheno DNA damage under normal and pathological conditions.

Effects of pesticides on DNA and protein of shrimp larvae Litopenaeus stylirostris of the California Gulf.

Recently, diverse pathologies and massive mortalities have been presented in shrimp hatcheries located along the California Gulf; therefore, toxic responses of shrimp larvae were used as biomarkers of pesticide pollution, because in this region intensive agriculture is practiced. Shrimp larvae were exposed to DDT, azinphosmethyl, permethrine, parathion, chlorpyrifos, malathion, endosulfan, and carbaryl, in order to determine LC50, DNA adducts and/or breaks, and total protein in larvae. The results indicate reductions in protein and DNA in larvae exposed to these pesticides, and in those exposed to DDT, breaks and/or adducts were registered. It is possible that pesticide pollution is a cause of these problems, because reduction in protein indicates a decrease in larvae growth rate and DNA breaks or adducts have been related to pathologies and carcinogenesis in many aquatic organisms.

Trends of polycyclic aromatic hydrocarbon levels and mutagenicity in Santiago's inhalable airborne particles in the period 1992-1996.

Trends of polycyclic aromatic hydrocarbons (PAHs) for 1992-1996 (cold season) and their mutagenic activity were investigated in organic extracts from the Santiago, Chile, inhalable particles (PM(10)). The highest PAH concentrations were observed in 1992 and declined dramatically in the following years. During this period, total PAHs decreased 85%, carcinogenic PAHs 82%, and benzo[a]pyrene, the most potent carcinogen, 85%. In spite of this significant decrease, PAH levels in respirable particles were higher than those reported in recent studies in Australia, Europe, and the United States. PAH profiles were analyzed by principal component (PC) analysis and Pearson correlation analysis. PC1 represents 71% of the variance, suggesting that most PAHs might originate predominantly from one main generic source. Higher correlations were obtained for the major carcinogenic PAHs. Most of the samples assayed were highly mutagenic to Salmonella typhimurium both in the presence and in the absence of metabolic activation system (S9), especially in the coarse fraction, but direct mutagenicity did not decline significantly. Incubation of calf thymus DNA with organic extracts from particulate matter and xanthine oxidase allowed the detection of five nitro-PAH-DNA adducts. Thus, nitroarenes might play an important role in the mutagenic activity of inhalable particles in Santiago, representing a high risk for human health.

Diphenylacetaldehyde-generated excited states promote damage to isolated rat liver mitochondrial DNA, phospholipids, and proteins.

This work studies damage to rat liver mitochondrial protein, lipid, and DNA caused by electronically excited states generated by cytochrome c-catalyzed diphenylacetaldehyde enol oxidation to triplet benzophenone. The extension of lipid peroxidation was estimated by production of thiobarbituric acid-reactive substances and by formation of Schiff bases with membrane proteins, evaluated by SDS-polyacrylamide gel electrophoresis. Concomitant with DPAA-driven mitochondrial permeabilization, extensive mtDNA fragmentation occurred and DNA adducts with aldehydes-products of fatty acid oxidation-were observed. The degree of lipid peroxidation and mtDNA alterations were significantly decreased by butylated hydroxytoluene, a potent peroxidation chain breaker. The lipid peroxidation process was also partially inhibited by the bioflavonoid rutin and urate totally prevented the mitochondrial transmembrane potential collapse. In all cases, the mitochondrial damage was dependent on the presence of phosphate ions, a putative bifunctional catalyst of carbonyl enolization. These data are consistent with the notion that triplet ketones may act like alkoxyl radicals as deleterious reactive oxygen species on biologic structures. Involvement of singlet dioxygen formed by triplet-triplet energy transfer from benzophenone in the model reaction with DPAA/cytochrome c in the presence of DCP liposomes was suggested by quenching of the accompanying chemiluminescence upon addition of histidine and lycopene.

Antioxidant actions of plant foods: use of oxidative DNA damage as a tool for studying antioxidant efficacy.

Plant-food-derived antioxidants and active principles such as flavonoids, hydroxycinnamates (ferulic acid, chlorogenic acids, vanillin etc.), beta-carotene and other carotenoids, vitamin E, vitamin C, or rosemary, sage, tea and numerous extracts are increasingly proposed as important dietary antioxidant factors. In this endeavor, assays involving oxidative DNA damage for characterizing the potential antioxidant actions are suggested as in vitro screens of antioxidant efficacy. The critical question is the bioavailability of the plant-derived antioxidants.

Proliferação celular induzida por 8-oxoguanosina e 8-metilguanosina, dois produtos do ataque de radicais livres a ribonucleosídeos e RNA / Cell proliferation induced by 8-oxoguanosine and 8-methylguanosine, two products of free radical attack to ribonucleosides and RNA

Os efeitos de ribonucleosídeos de guanina substituídos na posição C-8 na proliferação de linfócitos B estão bem documentados na literatura. Esses compostos são análogos de adutos formados pela adição de radicais livres a ribonucleosídeos e a RNA. Neste trabalho, verificamos as propriedades proliferativas de dois desses adutos, 8-metilguanosina (8-MeGuo) e 8-oxo-7 ,8-di-hidroguanosina (8-OxoGuo) e comparamos com 8-bromoguanosina (8-BrGuo), o composto mais estudado como indutor da proliferação de linfócitos B. 8-MeGuo e 8-OxoGuo foram sintetisados em rendimentos de 28 e 55%, respectivamente, e foram caracterizados por UV, NMR e CG-massa. Seus efeitos sobre a incorporação de timidina radioativa ([3H] TdR) no DNA de células de baço, fibroblasto 3T3(A31) e melanoma B16F10 foram examinados. Os dois adutos foram mitogênicos para células de baço mas foram seletivos quanto as células imortalizadas. 8-MeGuo atuou sobre células 3T3(A31) e 8-OxoGuo sobre as células de melanoma B16F10. O análogo não fisiológico 8-BrGuo foi efetivo em todas as células testadas. Experimentos de contagem de células, citotoxicidade e citometria de fluxo, indicaram que a síntese de DNA induzida pelas guanosinas substituídas na posição C-8 refletia crescimento celular. Foi proposto que os compostos agem de dentro da célula uma vez que seus efeitos são bloqueados em presença de um inibidor de transporte de nucleosídeo, mas não foram inibidos por um antagonista de receptor purinérgico. Os resultados obtidos, junto com os descritos na literatura, sugerem que no caso dos fibroblastos 3T3(A31) e células de baço de camundongo os efeitos proliferativos dos compostos não são dependentes do metabolismo desses compostos via salvação das purinas. No caso das células de melanoma, entretanto, os compostos parecem fazer parte do "pool" de nucleosídeos. A demonstração de que adutos produzidos por ataques radicalares em ribonucleosídeos e RNA são capazes de induzir proliferação celular, abre novas perspectivas para a compreensão do papel de radicais livres em processos carcinogênicos

The ability of CS-substituted guanine ribonucleosides to induce B cell proliferation has been well documented in the literature. These compounds are analogues of adducts formed from free radical attack on ribonucleosides and RNA. Here we examined the proliferative properties of two of these radical adducts, 8-methylguanosine (8-MeGuo) and 8-oxo-7 ,8-dihydroguanosine (8-OxoGuo) and compared them with those of the well studied B cell mitogen, 8-bromoguanosine (8-BrGuo). 8-MeGuo and 8-OxoGuo were synthesized in yields of 28 and 55 %, respectively, and were characterized by UV, NMR and CG-MS. Their effects upon [3H] thymidine uptake by Swiss mice splenocytes, mouse embryo 3T3 (A31) fibroblasts and mouse B16F10 melanocytes were examined. Both guanosine radical adducts were shown to increase [3H] thymidine uptake by mice splenocytes but displayed selectivity in regard to continuous cell lines. 8-MeGuo acted upon 3T3(A31) fibroblasts whereas 8-OxoGuo acted upon B16F10 melanocytes. The non physiological analogue 8-BrGuo acted upon all tested cells. Parallel experiments of cell counting, cytotoxicity, and cell sorting indicated that DNA synthesis induced by the C8-substituted guanosines reflected cell growth. It is proposed that the compounds act intracellularly because their proliferative effects were blocked in the presence of a nucleoside transport inhibitor but were not inhibited by an antagonist of the A2 purine receptor. The obtained results, taken together with data from the literature suggest that in the case of 3T3 (A31) fibroblasts and mice splenocytes the proliferative effects of the compounds are not dependent on metabolism through purine salvage pathways. In the case of melanocytes, however, the compounds are likely to become part of the purine nucleoside pool. The demonstration that adducts produced by free radical attack on ribonucleosides and RNA are able to induce cell proliferation opens new perspectives for the understanding of free radical mediated carcinogenesis

Tobacco smoking and cancer: the promise of molecular epidemiology.

Neoplastic development is a multistage process that includes multiple genetic changes. In this article the authors review studies on molecular epidemiology of tobacco. Current concepts of the multistage carcinogenic model are reviewed, as are their use in observational studies. Finally, benzo[a]pyrene are analyzed as an example.

Contaminación ambiental: uso de indicadores bioquímicos en evaluaciones de riesgo ecotoxicológico / Environmental pollution: applicability of biomarkers in ecotoxicological risk assessment

En el trabajo son analizadas las principales estrategias elaboradas y desarrolladas desde las Ciencias Ambientales para la estimación del efecto generado por la introducción de sustancias extrañas (xenobióticos) en sistemas naturales, es decir los análisis químicos cuantitativos, los estudios ecológicos, los bioensayos, los estudios de microcosmos o de mesocosmos, y la utilización de indicadores bioquímicos. En este contexto, son discutidas con mayor detalle las principales características -y consecuentemente potenciales aplicaciones- de aquellos indicadores de la presencia de contaminantes de tipo bioquímico y/o celular, agrupados bajo la denominación de "biomarcadores" (indicadores bioquímicos). Esquemáticamente los indicadores bioquímicos se caracterizan por presentar las siguientes propiedades: - evidenciar la presencia de contaminantes a niveles subletales; - integrar adecuadamente el efecto de la presencia de diversos xenobióticos asequibles para los organismos y sus respectivos metabolitos; - incorporar las interacciones toxicológicas y farmacodinámicas; - predecir las consecuencias derivadas del tiempo y la frecuencia de exposición. Finalmente se discute la utilidad de los indicadores bioquímicos en programas de monitoreo ambiental, y en la predicción del efecto de la contaminación sobre la integridad de las poblaciones o comunidades afectadas, al ser utilizados en forma complementaria con las otras estrategias presentadas

Contaminación ambiental: uso de indicadores bioquímicos en evaluaciones de riesgo ecotoxicológico / Environmental pollution: applicability of biomarkers in ecotoxicological risk assessment

En el trabajo son analizadas las principales estrategias elaboradas y desarrolladas desde las Ciencias Ambientales para la estimación del efecto generado por la introducción de sustancias extrañas (xenobióticos) en sistemas naturales, es decir los análisis químicos cuantitativos, los estudios ecológicos, los bioensayos, los estudios de microcosmos o de mesocosmos, y la utilización de indicadores bioquímicos. En este contexto, son discutidas con mayor detalle las principales características -y consecuentemente potenciales aplicaciones- de aquellos indicadores de la presencia de contaminantes de tipo bioquímico y/o celular, agrupados bajo la denominación de "biomarcadores" (indicadores bioquímicos). Esquemáticamente los indicadores bioquímicos se caracterizan por presentar las siguientes propiedades: - evidenciar la presencia de contaminantes a niveles subletales; - integrar adecuadamente el efecto de la presencia de diversos xenobióticos asequibles para los organismos y sus respectivos metabolitos; - incorporar las interacciones toxicológicas y farmacodinámicas; - predecir las consecuencias derivadas del tiempo y la frecuencia de exposición. Finalmente se discute la utilidad de los indicadores bioquímicos en programas de monitoreo ambiental, y en la predicción del efecto de la contaminación sobre la integridad de las poblaciones o comunidades afectadas, al ser utilizados en forma complementaria con las otras estrategias presentadas (AU)