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Consensus statements from the Second International Lung Cancer Molecular Biomarkers Workshop: a European strategy for developing lung cancer molecular diagnostics in high risk populations.

The Second Molecular Biomarkers Workshop was held at the Roy Castle International Centre for Lung Cancer Research in Liverpool, in June 2001 and it brought together experts in the clinical, epidemiological and molecular-pathology of lung cancer from Europe and the USA, to address issues surrounding the development of a European strategy for early lung cancer detection. The 2001 Workshop Breakout Groups concentrated on the current challenges in the early detection of lung cancer which need to be addressed in the light of the recent surge in interest in many countries for mounting new clinical trials to evaluate the utility of Spiral CT in early lung cancer detection. If population-based trials of CT screening are mounted it will also be a favorable clinical environment in which to evaluate efficiently recent advances in molecular screening and genotyping. The Workshop focused specifically on: a) clinical and molecular biomarkers, b) sputum as an early detection and diagnostic tool, c) validation of molecular markers prior to their use in early detection trials and d) ethical issues that have to be considered in early lung cancer detection trials. A distillation of the Workshop discussions is given in this article.

Biomarkers, Tumor↗

Assessing the health of grass shrimp (Palaeomonetes pugio) exposed to natural and anthropogenic stressors: a molecular biomarker system.

We developed a molecular biomarker system (MBS) to assess the physiological status of Palaomenetes pugio (grass shrimp) challenged with exposure to heat stress, cadmium, atrazine, and the water-accommodating fraction of either diesel fuel or bunker fuel No. 2. The MBS assayed 9 specific cellular parameters of shrimp that are indicative of a nonstressed or stressed condition: heat-shock protein 60, heat-shock protein 70, alpha B-crystallin homologue, lipid peroxide, total glutathione level, ubiquitin, mitochondrial manganese superoxide dismutase, metallothionein, and cytochrome P-450 2E homologue. Using these 9 parameters, the MBS can distinguish between the responses to each stressor, and to the nonstressed control conditions. The MBS was able to determine the structural integrity of the cell as defined by protein turnover, protein chaperoning, and lipid composition via lipid peroxide levels, and the status of key metabolic processes such as cytoskeletal integrity and glutathione redox potential. This technology aids in the accurate diagnosis of the health of shrimp because the physiological significance of changes of each parameter is well known. This technology is particularly relevant for environmental monitoring because grass shrimp are used as key indicator species in many estuarine ecosystems. Finally, this system is easy to implement, precise, and can be quickly adapted to an automated high-throughput system for mass sample analysis.

Journal Article↗

[Molecular biomarkers in cancer: implications for epidemiological research and public health].

Identification of molecular biomarkers is a common result of current cancer epidemiological research. Both genetic and molecular epidemiology have enjoyed impressive developments in recent decades, with important repercussions on traditional epidemiological approaches. In this paper we evaluate the new frontiers of cancer epidemiology, incorporating both genetic and molecular biology approaches. We examine the current knowledge of molecular biomarkers for exposure and susceptibility to cancer, the role of gene mutations in carcinogenesis, and their application to epidemiological studies. By exploring the status of relevant biomarkers, these approaches become effective in evaluating exposure and susceptibility and show enormous potential for elucidating mechanisms of carcinogenesis and the effect of risk factors in cancer. However, these approaches are necessarily more invasive and raise several ethical issues for consideration by both researchers in public health and society as a whole.

Environmental Exposure↗

A study of the relationship between molecular biomarkers of joint degeneration and the magnetic resonance-measured characteristics of cartilage in 16 symptomatic knees.

We used quantitative magnetic resonance (MR) imaging to determine if relationships exist between proposed molecular biomarkers for degenerative joint disease (DJD) and structural characteristics of articular cartilage. Subjects were eight male and eight female volunteers diagnosed with osteoarthritis. Magnetic resonance images of the symptomatic knee were taken and blood samples were drawn. Concentrations of serum cartilage oligomeric matrix protein (COMP) and cleaved collagen neoepitope were compared to cartilage volume and cartilage T2, respectively, in four compartments of the tibiofemoral joint. A significant, negative correlation was found between serum COMP and medial tibia volume in the male subject group (rho=-.738, P=.037). A significant, positive correlation (rho=.881, P=.0039) was found between serum COMP and lateral femur volume in the female subject group. In both groups, positive correlations were found between serum C2C and cartilage T2, which were significant in two compartments of the male group (rho=.714, P=.047; rho=.738, P=.037) and similarly strong, but not statistically significant (rho=.750, P=.052), in one compartment of the female group. We identify strong and biologically relevant correlations between two proposed molecular biomarkers for DJD and MR measures of symptomatic knees of a small number of arthritic patients. Our findings support the hypothesis that cartilage molecular biomarkers reflect the molecular processes of cartilage degeneration and loss.

Adult↗

Predictive testing of early CIN behaviour by molecular biomarkers.

Each year, 330,000 new Cervical Intraepithelial Neoplasias(CIN) occur in the European Union (EU) of which 120,000 are early CIN where grade (1, 2) indicates the progression-risk to CIN-3 and therefore determines the treatment choice. However, the Positive Predictive Value (PPV) of CIN grade to predict progression is low (10% and 20% for CIN-1 and -2 respectively, 16% on average) resulting in an enormous number of over-treatments indicating worrisome grade reproducibility.Certain molecular biomarkers such as Ki-67 have a higher PPV (30%, an improvement of 14%), which in Europe alone could improve treatment for many thousands of women per year with considerable cost reduction for the health care system. The quantitative Ki-67 prognostic model has been validated in independent retrospective and prospective studies from different laboratories. Moreover, the PPV of Ki-67 alone can be improved by additional molecular biomarkers (retinoblastoma protein = Rb, cytokeratins= CK-14/-13). Combined Ki67-Rb allows a 2-tiered progression-risk subgroup assignment as very low ( approximately 0% progression, 71% of all CIN-I/II patients)and high risk (48% progression risk, incidence 32%), leaving a small (7% of all) prognostically undetermined group (17% progression). Additional CK-14 and -13 analysis can sub-classify the high-risk in an intermediate and very high risk subgroup(with 40% and 100% progression risks respectively).Thus, molecular biomarkers are potentially important determinators of early CIN lesion behaviour. Important factors for widespread acceptance of molecular biomarkers are (1) market penetration by user-friendly equipment, (2) (inter)national keeping of GLP conditions (reproducibility, independent validation), requiring customer-driven industrial efforts,governmental measures, and additional PPV improvement to further reduce over-treatment.

Biomarkers, Tumor↗

Molecular biomarker profiling in noninfectious uveitis: a chronological review of discovery.

PURPOSE OR REVIEW: Noninfectious uveitis (NIU) encompasses a heterogeneous group of immune-mediated intraocular inflammatory diseases whose complexity has driven systematic molecular biomarker discovery. This review presents NIU molecular biomarkers organized by biological category; autoantigens, human leukocyte antigens (HLA) and genetic markers, cellular immune subsets, cytokines, chemokines, and multiomics platforms including proteomics, microbiome metagenomics, metabolomics, and single-cell transcriptomics with each category presented in strict chronological order of landmark discovery. RECENT FINDINGS: We present a review organized along two nested timelines. Categories are presented in the order they historically emerged in the field, and within each category, landmark discoveries appear in chronological sequence. This allows the reader to trace how each biomarker category evolved: from foundational autoantigen identification in experimental uveitis models, through the genomic revolution of HLA association studies, into cellular immunophenotyping, cytokine profiling of aqueous humor, chemokine mapping of intraocular trafficking, and finally the emerging omics platforms that may potentially anchor precision medicine in NIU. Each biomarker is paired in line with its linked targeted therapeutic. SUMMARY: Biomarker research has transformed the understanding of NIU from a clinically defined syndrome into a group of molecularly distinct immune disorders. Advances spanning autoantigens, genetics, immune-cell profiling, cytokines, chemokines, and multiomics have revealed novel pathogenic mechanisms and therapeutic targets. Integration of these biomarkers with targeted therapies may accelerate the transition toward precision medicine in uveitis care.

cytokines↗

Molecular biomarkers and adaptation to environmental stress in moon jelly (Aurelia spp.).

We describe a strategy that identifies molecular biomarkers and links the study of abiotic stress to evolutionary history. By utilizing the moon jellyfish Aurelia spp. as a model, we identified genes differentially regulated in response to the chemical stressor tributyltin by means of complementary DNA subtraction analyses. Expression of 3 out of 25 identified candidate genes, one oxidative stress gene, one heat shock (hsp70) gene, and one GTP-binding gene, was quantified under laboratory conditions and in field tests using semiquantitative reverse transcriptase polymerase chain reaction. Differential expression patterns were found following exposure to tributyltin and temperature treatments. The findings suggest that the identified genes are involved in response to chemical as well as heat- induced stress and may serve as biomarkers for monitoring marine habitats. Gene regulatory patterns combined with phylogenetic inferences of the hsp70 gene support a possible role of ecologically driven divergence within the genus Aurelia. We show that added information on genetic variability can raise the predictive power of molecular biomarkers in studies of individual stress response.

Adaptation, Biological↗

Evaluation of stress-inducible hsp90 gene expression as a potential molecular biomarker in Xenopus laevis.

In this study we have evaluated stress-inducible hsp90 mRNA accumulation as a potential molecular biomarker in Xenopus laevis. In order to obtain a probe for Northern blot analysis we employed a PCR-based approach using degenerate primers for the amplification and cloning of an hsp90 gene sequence from Xenopus laevis. The deduced amino acid sequence is 102 amino acids in length and exhibited the highest degree of identity with zebrafish and human hsp90 beta genes. Furthermore, the putative intron and exon boundaries of this fragment are the same as hsp90 beta in chicken, mouse and human, indicating that the fragment represents a Xenopus hsp90 beta-like gene. Northern blot analyses revealed that this gene was constitutively expressed in cultured A6 cells. While heat shock and sodium arsenite exposure resulted in the increased accumulation of hsp90 mRNA in A6 cells, treatment with cadmium chloride and zinc chloride did not. Also, exposure of A6 cells to concurrent heat shock and sodium arsenite produced a mild synergistic response with respect to hsp90 mRNA levels in contrast to hsp70 mRNA levels which displayed a strong synergistic effect. Finally, hsp90 mRNA was detected constitutively throughout early embryogenesis but was heat-inducible only in late blastula and later stages of development. Given the normal abundance and limited stress-induced accumulation of hsp90 mRNA, it may not have a great deal of potential as a molecular biomarker compared to hsp70 and hsp30 mRNA. However, it may be useful in conjunction with other stress protein mRNAs to establish a set of biomarker profiles to characterize the cellular response to a stressful or toxic agent.

Amino Acid Sequence↗

A molecular biomarker system for assessing the health of gastropods (Ilyanassa obsoleta) exposed to natural and anthropogenic stressors.

We developed a Molecular Biomarker System (MBS) to assess the physiological status of mud snails (Ilyanassa obsoleta) challenged by exposure to high temperature, cadmium, atrazine, endosulfan and the water-accommodating fraction of bunker fuel #2. The MBS is used to assay specific cellular parameters of the gastropod cell that are indicative of a non-stressed or stressed condition. The MBS distinguished among responses to each stressor and to non-stressed control conditions. For example, the biomarkers metallothionein and cytochrome P450 2E1 homologue distinguished between metal and non-metal stresses. MBS data from this study corroborate toxicological studies of organismal responses to endosulfan, atrazine, fuel and cadmium stresses. The MBS technology aids in the accurate diagnosis of the snail's health condition because the physiological significance of the changes of each biomarker is well known. This technology is particularly relevant for environmental monitoring because gastropods are used as key indicator species in many estuarine, marine, freshwater and terrestrial ecosystems. Finally, the Molecular Biomarker System technology is relatively inexpensive, easy to implement, precise and can be quickly adapted to an automated, high-throughput system for large sample analysis.

Journal Article↗

Molecular biomarkers for aflatoxins and their application to human cancer prevention.

The rapidly expanding understanding of the progressive processes of carcinogenesis provides opportunities for the identification of molecular biological markers reflecting events from exposure through clinical disease. These molecular biological markers can be classified into categories of markers of exposure reflecting the dose of toxic agents, markers of effect indicating a biological response to exposure, and markers of susceptibility providing information about the inherent sensitivity of individuals to the toxic agents. By definition some of these markers are chemical agent specific, such as a carcinogen-DNA or -protein adduct, while others are biological process specific, such as the altered expression of a gene. This article reviews the development and validation of molecular biomarkers of aflatoxins using experimental and human population studies. The development of molecular biomarkers for aflatoxins is based upon the extensive research database available about their metabolism, macromolecular adduct formation, and general mechanisms of action. The long-term goal of the research described in this paper is the application of aflatoxin biomarkers to the development of preventive interventions in human populations at high risk for liver cancer.

Aflatoxins↗

P16 as a molecular biomarker of cervical adenocarcinoma.

OBJECTIVE: Cervical adenocarcinomas are increasing in incidence each year. The aim of this study was to identify a molecular biomarker to improve early detection. STUDY DESIGN: Fifty-five in situ and invasive cervical adenocarcinomas were compared with 5 normal endocervical controls by immunohistochemical analysis of p16, p21, p27, cyclin D1, cyclin E, p53, and Ki-67. Expression was scored from 0 to 8 by using an automated imaging system. Western blotting and polymerase chain reaction-based human papillomavirus (HPV) testing were performed on 16 of the invasive cases having fresh-frozen tissue. RESULTS: P16 exhibited a higher mean expression score for in situ (7.4; P<.0001) and invasive cervical adenocarcinoma (6.6; P<.0001) versus controls (2.0). A cutoff p16 expression score of 5 had a sensitivity of 94.5% and a specificity of 100%. Western blotting confirmed p16 protein expression. Fourteen (88%) of 16 invasive cervical adenocarcinomas were HPV-positive. CONCLUSION: P16 is a putative molecular biomarker of cervical adenocarcinoma. Overexpression appears to primarily reflect HPV-induced cell cycle dysregulation.

Adenocarcinoma↗

Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer--a plan to move forward.

This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.

Biomarkers, Tumor↗

Molecular biomarkers for breast cancer prognosis: coexpression of c-erbB-2 and p53.

OBJECTIVE: To assess the prognostic significance of molecular biomarkers, particularly c-erbB-2 and p53, through study of prospective clinical data and archival breast cancer tissues for women accrued to the Alabama Breast Cancer Project. SUMMARY BACKGROUND DATA: Defining molecular abnormalities in breast cancer is an important strategy for early detection, assessment of prognosis, and treatment selection. Evidence is strong that selective biomarkers, including c-erbB-2 and p53, have prognostic significance in breast cancer. Few studies have analyzed the prognostic significance of coexpression of biomarkers. METHODS: Study patients were those accrued to the Alabama Breast Cancer Project (1975-1978) who had archival breast cancer tissues available for analysis. Criteria for entrance into the Alabama Breast Cancer Project were T1-3 breast cancer with M0 status. Age, nodal status, and histologic grade were also documented. Patients were randomized to radical versus modified radical mastectomy, and node-positive patients were also randomized to adjuvant chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) versus melphalan. Archival breast cancer tissues were studied for c-erbB-2, TGF-alpha, p53, cathepsin D, bcl-2, and estrogen and progesterone receptor expression using immunohistochemistry. Survival curves were developed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, multivariate analysis using a rank regression model. RESULTS: Three hundred eleven patients were accrued to the Alabama Breast Cancer Project, and paraffin-embedded breast cancer tissues for 90 patients were available for immunohistochemical analysis of molecular biomarkers. Univariate analysis showed nodal status, c-erbB-2 expression, and p53 expression to have prognostic significance. Coexpression of c-erbB-2 and p53 was also found to have prognostic significance by the log-rank test. Multivariate analysis showed T stage, nodal status, c-erbB-2 expression, and p53 expression to have independent prognostic significance. CONCLUSIONS: These data suggest that c-erbB-2 and p53 expression in breast cancer have prognostic significance. After median follow-up of 16 years, coexpression of c-erbB-2 and p53 may have more prognostic significance than traditional prognostic factors such as T stage and nodal status. Prospective study of large numbers of patients with breast cancer is encouraged to validate these findings.

Aged↗

[Molecular cytopathology of lung cancer--prevalence of genetic alterations and their role in the development of molecular biomarkers].

Carcinogenesis of lung cancer proceeds via a complex process that involves multiple genetic abnormalities, which do not necessarily have a linear progression. Genetic alterations include aneuploidy, deletions and amplifications of chromosomal regions, loss of heterozygosity (LOH), microsatellite alterations, point mutations and aberrant promoter methylation. There is considerable effort to use these genetic alterations as molecular biomarkers for early cancer diagnosis applying different approaches. An ideal tumor marker should be highly sensitive, tumor specific, easily to handle and non-cost intensive. While previous studies used screening for mutations, LOH and microsatellite alterations, more recent strategies concentrate on multicolor fluorescence in situ hybridization (FISH) and aberrant promoter methylation. Since in general the genetic alterations are prone to be more extensive in tumor cells as compared to non-tumor cells, methods that provide quantitative data (e.g., methylation specific real-time PCR) are likely to improve specificity. Consequently, molecular biomarkers could constribute to a more accurate risk assessment in carcinogen exposed individuals and early molecular cytologic diagnosis of precancerous lesions and cancers of the lung.

Allelic Imbalance↗

Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: identification of novel molecular biomarkers for early diagnosis and therapy.

OBJECTIVE: To identify novel molecular biomarkers useful for the early diagnosis and therapy of ovarian cancer by gene expression profiling. To compare the genetic fingerprints of flash-frozen ovarian serous carcinomas to those of matched highly purified primary tumor cell cultures. METHODS: Gene expression profiles of 19 flash-frozen ovarian serous papillary carcinoma (OSPC) were analyzed and compared to 15 controls (highly purified human ovarian surface epithelium short-term cultures, HOSE) using oligonucleotide microarrays complementary to >14,500 human genes. In addition, gene expression profiling of 5 highly purified primary OSPC cultured in vitro for less than 2 weeks was compared to flash-frozen ovarian carcinoma biopsies obtained from matched samples. Quantitative RT-PCR and IHC staining techniques were used to validate microarray data at RNA and protein levels for some of the differentially expressed genes. RESULTS: Unsupervised analysis of gene expression data readily distinguished normal tissue from flash-frozen OSPC and identified 901 and 557 genes that exhibited >3-fold up-regulation or down-regulation, respectively, in OSPC when compared to HOSE. Mammaglobin 2, an ovarian secreted protein, was identified as the top differentially expressed gene in OSPC (19 out 19 OSPC versus 0 out of 15 HOSE) with over 827-fold up-regulation relative to HOSE. The claudin and kallikrein family of proteins including the clostridium perfringens enterotoxin receptors claudin 3 and 4, kallikreins 6, 7, 8, 10, 11 and the immunomodulatory molecule B7-H4 were found among the most highly overexpressed genes in OSPC when compared to HOSE. Genetic fingerprints of flash-frozen OSPC were found to have high correlation with those of purified primary OSPC short-term in vitro cultures with only 31 out of 8,637 genes (0.35%) differentially expressed between the two groups. CONCLUSIONS: Short-term in vitro culture of primary ovarian carcinomas may greatly increase the purity of ovarian tumor RNA available for gene expression profiling without causing major alteration in OSPC fingerprints. Mammaglobin 2, kallikreins 6, 7, 8, 10, 11, claudin 3 and 4 and B7-H4 gene expression products represent candidate biomarkers endowed with great potential for early screening and therapy of OSPC patients.

Adult↗

Nasopharyngeal carcinoma: molecular biomarker discovery and progress.

Nasopharyngeal carcinoma (NPC) is a rare malignancy in most part of the world and it is one of the most confusing, commonly misdiagnosed and poorly understood diseases. The cancer is an Epstein-Barr virus-associated malignancy with a remarkable racial and geographical distribution. It is highly prevalent in southern Asia where the disease occurs at a prevalence about a 100-fold higher compared with other populations not at risk. The etiology of NPC is thought to be associated with a complex interaction of genetic, viral, environmental and dietary factors. Thanks to the advancements in genomics, proteomics and bioinformatics in recent decades, more understanding of the disease etiology, carcinogenesis and progression has been gained. Research into these components may unravel the pathways in NPC development and potentially decipher the molecular characteristics of the malignancy. In the era of molecular medicine, specific treatment to the potential target using technologies such as immunotherapy and RNAi becomes formulating from bench to bedside application and thus makes molecular biomarker discovery more meaningful for NPC management. In this article, the latest molecular biomarker discovery and progress in NPC is reviewed with respect to the diagnosis, monitoring, treatment and prognostication of the disease.

Biomarkers↗

Screening of molecular biomarkers ASPN and LBH and construction of a prediction nomogram for the progression of esophagogastric junction adenocarcinoma.

BACKGROUND: Esophagogastric junction adenocarcinoma (EGJA) is an aggressive malignancy of the digestive system with poor prognosis. Early diagnosis and accurate prediction of tumor progression remain major clinical challenges. This study aimed to identify and validate molecular biomarkers and construct a precise diagnostic model, providing a scientific basis for individualized treatment. METHODS: Differentially expressed genes (DEGs) associated with EGJA were identified using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was then performed for further screening. The protein expression levels of ASPN and LBH were validated by immunohistochemistry in both tumor and adjacent non-tumor tissues. A nomogram was constructed by integrating clinical and pathological features, and its performance and clinical utility were assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS: Immunohistochemistry demonstrated that the protein expression of ASPN was significantly upregulated in tumor tissues, with expression levels increasing with tumor stage. Conversely, LBH was downregulated in tumor tissues and decreased with advancing stages. The predictive model achieved an area under the curve (AUC) value of 0.977, indicating excellent diagnostic and prognostic performance. DCA confirmed the clinical net benefit of the model. CONCLUSIONS: ASPN and LBH are critical molecular biomarkers for EGJA. The nomogram combining these two markers enables accurate distinction between early and advanced-stage tumors, offering significant support for early diagnosis of EGJA.

ASPN↗

Laboratory and field validation of multiple molecular biomarkers of contaminant exposure in rainbow trout (Oncorhynchus mykiss).

Novel primers for three different genes (CYP1A1, vitellogenin, and metallothionein) for use in reverse transcription-polymerase chain reaction (RT-PCR) were developed and tested in laboratory flow-through experiments using model compounds benzo[a]pyrene, estradiol, and cadmium. Field validations of the molecular biomarkers were performed using 8-d or 48-h in situ, cagedexposure of juvenile rainbow trout (Oncorhynchus mykiss). Expression levels of genetranscription(messengerRNA [mRNA]) were monitored in gill and liver tissue after exposure at sites downstream of a known source of creosote contamination in the Little Scioto River (Marion, OH, USA) and metals and hydrocarbon contamination in Dick's Creek (Middletown, OH, USA). Significant increases of liver cytochrome P4501A1 gene (CYP1A1) and vitellogenin were measured in both streams at sites downstream of contaminant sources. Significant increases of gill CYP1A1 were also observed. Significant increases of gill and livermetallothionein occurred in Dick's Creek. A sample of gill tissue taken from each fish prior to placement in the Little Scioto River provided a pre-exposure control measurement for each individual. Expression of CYP1A1 and vitellogenin in trout at both streams indicated that exposure to bioavailable hydrocarbons and endocrine-disrupting compounds had taken place. Previous to this study, estrogenic compounds had not been detected in the Little Scioto River. Metallothionein expression confirmed the presence of metals in Dick's Creek. These results suggest a mixed contaminant environment that poses physiological hazard to existing teleost populations. Multiple molecular biomarkers provided a sensitive, physiologically based method of determining contaminant presence and bioavailability to aquatic organisms.

Animals↗