PubMed Health⌕ Search

Biomedical subjects

C W Theodorakis

Publications and source records attributed to C W Theodorakis.

7 recordsLinked to original sources

Comparative acute and combinative toxicity of aflatoxin B1 and fumonisin B1 in animals and human cells.

Aflatoxin B(1) (AFB(1)) and fumonisin B(1) (FB(1)) are important food-borne mycotoxins. The co-contamination of food stuffs with these two mycotoxins is well known and has been possibly implicated in the development of human hepatocellular carcinoma in high risk regions around the world. In this study the acute and combinative toxicity of AFB(1) and FB(1) were tested in F-344 rats, mosquitofish (Gambusia affinis), immortalized human hepatoma cells (HepG2) and human bronchial epithelial cells (BEAS-2B). Preliminary experiments were conducted in order to assess the acute toxicity and obtain LD(50), LC(50) and IC(50) values for individual toxins in each model, respectively. This was followed by testing combinations of AFB(1) and FB(1) to obtain LD(50), LC(50) and IC(50) values for the combination in each model. All models demonstrated a significant dose response in relation to toxin treatment. The potency of the mixture was gauged through the determination of the interaction index metric. Results of this study demonstrate that these two toxins interacted to produce alterations in the toxic responses with a strong additive interaction noted in the cases of F344 rats and mosquitofish. It can be gathered that this combination may pose a significant threat to public health and further research needs to be completed addressing alterations in metabolism and detoxification that may influence the toxic manifestations in combination. These results will provide foundational knowledge for future studies on long-term combinative toxic and health effects of these mycotoxins.

Aflatoxin B1↗

Integration of genotoxic and population genetic endpoints in biomonitoring and risk assessment.

Genetic ecotoxicology is a multifaceted discipline that examines the effects of xenobiotic compounds on the structure and function of DNA. This paper discusses the role of genetic ecotoxicology in environmental biomonitoring and risk assessment. Genetic ecotoxicology may include somatic effects (e.g., DNA damage) or population genetic effects (changes in genetic diversity or gene frequencies). Traditionally, genetic ecotoxicology studies have focused on either one of these sub-disciplines, but integration of these two approaches would be advantageous for three reasons. First, at the population level, concordant responses between changes in population genetic structure and elevated levels of DNA damage may provide evidence that the population genetic changes are influenced by exposure to genotoxic chemicals. Second, if the frequencies of alleles or other genetic markers differ between genotoxicant-contaminated and reference populations, associations between relative amount of DNA damage and genotype may provide evidence that these changes are due to genotoxicant-induced selection. Third, genetic analysis of gene flow may provide insight into patterns of dispersal that could obscure differences between contaminated and reference populations. In order to demonstrate the application of these ideas, three lines of research are summarized herein. The first is a series of studies that focus on radionuclide-contaminated populations of mosquitofish (Gambusia). This research identified RAPD markers that may be indicative of genetic adaptation to radionuclide stress. Relative amounts of DNA damage among genotypes presented evidence that these markers may be indicators of relative radioresistance. The second study examined DNA damage and population genetic structure in radionuclide-contaminated kangaroo rat (Dipodomys) populations. It was found that between-population differences in genetic diversity paralleled those for DNA damage and relative levels of contamination. Also, population genetic analysis indicated that there was dispersal between contaminated and reference populations, and that between-population differences in the amount of DNA damage could not be detected until this dispersal was taken into account. In the third study, populations of redbreast sunfish (Lepomis auritris) from streams contaminated with complex mixtures of industrial chemicals were examined. It was found that the genetic distances between populations within the contaminated stream corresponded with the relative magnitude of molecular and community-level effects. It was concluded that genetic ecotoxicology could make significant contributions to the fields of environmental biomonitoring and ecological risk assessment, and that integration of genotoxicology and population genetic studies would be a definite advantage toward this end.

Animals↗

Preliminary assessment of perchlorate in ecological receptors at the Longhorn Army Ammunition Plant (LHAAP), Karnack, Texas.

There have been increasing human health and ecological concerns about ionic perchlorate (ClO4-) since it was detected in drinking water sources in 1997. Perchlorate is known to affect thyroid function, causing subsequent hormone disruption and potential perturbations of metabolic activities. According to current estimates, perchlorate is found in the surface of groundwater of 14 states, including Texas. Longhorn Army Ammunition Plant, located in east central Texas, was a facility historically associated with perchlorate-containing propellants and rocket motors. Subsequently, perchlorate contamination in ground and surface waters at the facility has been reported. Soil, sediment, water, vegetation, and animal tissue samples were collected from several locations within the plant for a preliminary site assessment of perchlorate contamination. Perchlorate concentrations ranged from 555-5,557,000 ppb in vegetation, 811-2038 ppb in aquatic insects, below detection limits (ND) to 207 ppb in fish, ND-580 ppb in frogs, and ND-2328 ppb in mammals. Consistent with our hypothesis, aquatic organisms inhabiting perchlorate-contaminated surface water bodies contained detectable concentrations of perchlorate. Additionally, terrestrial organisms were exposed through pathways not necessarily related to contaminated surface waters. Therefore, these data demonstrate that aquatic and terrestrial species are exposed to perchlorate in the environment. To our knowledge, this represents the first incidence of perchlorate exposure among wild animals reported in the scientific literature.

Amphibians↗

Integration of genotoxicity and population genetic analyses in kangaroo rats (Dipodomys merriami) exposed to radionuclide contamination at the Nevada Test Site, USA.

We examined effects of radionuclide exposure at two atomic blast sites on kangaroo rats (Dipodomys merriami) at the Nevada Test Site, Nevada, USA, using genotoxicity and population genetic analyses. We assessed chromosome damage by micronucleus and flow cytometric assays and genetic variation by randomly amplified polymorphic DNA (RAPD) and mitochondrial DNA (mtDNA) analyses. The RAPD analysis showed no population structure, but mtDNA exhibited differentiation among and within populations. Genotoxicity effects were not observed when all individuals were analyzed. However, individuals with mtDNA haplotypes unique to the contaminated sites had greater chromosomal damage than contaminated-site individuals with haplotypes shared with reference sites. When interpopulation comparisons used individuals with unique haplotypes, one contaminated site had greater levels of chromosome damage than one or both of the reference sites. We hypothesize that shared-haplotype individuals are potential migrants and that unique-haplotye individuals are potential long-term residents. A parsimony approach was used to estimate the minimum number of migration events necessary to explain the haplotype distributions on a phylogenetic tree. The observed predominance of migration events into the contaminated sites supported our migration hypothesis. We conclude the atomic blast sites are ecological sinks and that immigration masks the genotoxic effects of radiation on the resident populations.

Animals↗