There has been recent interest in the possible carcinogenic potential of vegetable fibers (plant fibers) containing amorphous silica. These fibers referred to as Biogenic Amorphous Silica Fibers (BAS) are the normal constituents of number of plant species such as sugar cane, wheat, barley, oats, rice etc. Exposure to fibers within the respirable range has been documented during sugar cane and rice farming and processing operations. Some studies have suggested that such exposure could increase the risk for lung cancer while others have suggested the contrary. In countries like India, sugar cane farming is the major occupation in a number of provinces. A large workforce is involved in its farming and processing. In order to investigate the risk for lung cancer among one such population in Western Maharashtra, we carried out a hospital-based case-control study in the region. As part of this study we measured the exposures to BAS fibers during the harvesting of the sugar cane and the processing of the cane in the mills. / Cases of lung cancer were ascertained from 6 cancer treatment centers and matched to controls who had other types of cancers on age, sex, area of residence and timing of diagnosis. After controlling for potential confounding variables such as smoking, asbestos exposure, family history of lung cancer, income, education and farming of other crops, the risk for lung cancer was elevated in workers involved in the farming of the sugar cane, Odds ratio (OR) 1.92; 95% Confidence Interval (CI) 1.08--3.40. Specifically, the risks were elevated for those involved in the preparation of the farm (OR: 1.81; 95% CI: 0.99--3.27) and in the burning of the farms after harvesting (OR: 1.82; 95% CI: 0.99--3.34). Risks were moderately elevated for those involved in the harvesting of the crop (OR: 1.41; 95% CI: 0.70--2.90) and in the processing of the crop in the sugar mills (OR: 1.70; 95% CI: 0.20--12.60). Smoking modified the relationship between sugar cane farming and lung cancer. Sugar cane farmers who smoked had a 6-fold higher risk compared to those who never farmed and did not smoke. / Environmental measures both during harvesting and processing of the crop in the mills showed exposure to vegetable fibers. Some of these fibers contained silica and resembled BAS fibers in morphology. However a majority of the fibers lacked mineral content and were unlikely to be those of BAS. / The epidemiological study showed increased risk for lung cancer among sugar cane farmers but the limited exposure data did not show high concentration of BAS fibers. The role of polynuclear aromatic hydrocarbons and crystalline silica in particular needs to explored in future studies.

Birth defects seen after teratogen exposure depend on the nature of the insult and the stage of development of the embryo. Many teratogens induce DNA damage in the organogenesis-stage conceptus; the consequences of this insult depend on the extent of the damage and on the ability of the embryo to repair DNA. The hypothesis for this thesis is that DNA repair capacity plays a role in the response of the conceptus to DNA-damaging teratogens. The first objective of this thesis was to elucidate the expression profile of DNA repair pathway genes during mid-organogenesis (gestational days 10--12) in the rat, a period during which the conceptus is most susceptible to the malformations induced by genotoxic teratogens. Four main repair pathways were examined: the nucleotide excision repair, base excision repair, mismatch repair, and recombination repair pathways. The genotoxic stress-activated cell cycle checkpoint pathway was also examined. Genes from these pathways showed developmental time-specific alterations in transcript and protein levels, as well as activity. Differences in expression between yolk sac and embryo proper were observed at the transcript, protein, and activity levels. / The second goal of this thesis was to determine whether DNA repair machinery expression and activity are modified in the conceptus following exposure to teratogens. Changes in gene transcript, protein, and activity levels were observed following embryo culture with three known teratogens (cyclophosphamide, oxidative stress, methotrexate). While one base excision repair gene increased in expression, the remaining repair genes examined either did not change transcript levels or decreased in expression following teratogen exposure, indicating a near complete inability to induce a DNA repair response following genotoxic stress. These results demonstrate that differential expression and regulation of DNA repair genes and gene products exist in the mid-organogenesis stage rat conceptus, and that the conceptus has a limited capacity to alter DNA repair responses at the transcript, protein, or activity level following genotoxic teratogen exposure.

<p> Predicting impact of oil spills on aquatic life requires a better understanding of effects on aquatic organisms, both for single hydrocarbons and for their interactions. In this study, the individual and combined effects of petroleum hydrocarbons phenanthrene (Phen) and dibenzothiophene (DBT) were assessed on the reproductive behavior of the freshwater amphipod <i>Hyalella azteca. </i> Following a 24-h exposure to single PAHs, or an equimolar mixture of Phen-DBT, mate-guarding behavior was assessed at the end of the exposure and during a subsequent 10 min behavioral observation period with the animals in clean water. The endpoints of the study during the behavior observation period were&mdash;time taken to initiate mate-guarding (TIMG), and proportion of time spent in amplexus (PTA). The study demonstrated that the exposure to Phen and DBT reduced the incidence of mate-guarding during the actual exposure period, but not during the observation period. However, whether or not pairs were involved in mate-guarding at the end of the exposure period did affect both TIMG and PTA during the observation period. Thus, the effects of Phen and DBT on amplexus status at the end of the exposure period indirectly affected TIMG and PTA during the observation period. The interaction between Phen and DBT with respect to their effects on mate-guarding varied among the mate-guarding measures. For the amplexus status at the end of the exposure period and for the effect on TIMG, the interaction did not deviate statistically from an additive effect. For PTA, the overall interaction was a synergistic one. This study's findings point out that assessments of hydrocarbon toxicity need to take into account that subtle reproductive behaviors (that may play an important role in population persistence) may be negatively affected. The results also show that the general assumption of additive effects among different PAHs may be an oversimplification.</p>

<p>Aquatic environments adjacent to industrialized urban centers typically contain anthropogenic chemicals that may cause disruption of endocrine systems and physiological functions. This study investigated whether sites within San Francisco Bay are associated with endocrine disruption in the indigenous fish, shiner perch. The endocrine system that produces cortisol was tested, since it is critical for physiological regulation of stress response, metabolism, immune function and osmoregulation. The cortisol-producing tissue, the interrenal, was also investigated using proteomics technologies to initiate a process of identifying proteins with altered expression and which may therefore be involved in tissue dysfunction. Disrupted cortisol responses were detected in fish from several locations and they were related to certain kinds of contaminants and to changed expression of at least four interrenal proteins, which include heat shock protein 1, transferrin, calreticulin, and calmodulin. Several interrenal proteins were also newly identified. The approaches used herein have strong prospects as bioanalytical screening methodologies in environmental studies. </p>

Excessive free radical formation or antioxidant enzyme deficiency can result in oxidative stress, a mechanism proposed in the toxicity of MPTP and in the etiology of Parkinson's disease (PD). To be effective as a toxin, MPTP must be metabolized by monoamine oxidase-B (MAO-B) to form MPP$ sp+.$ The latter compound leads to the degeneration of the dopaminergic cell bodies of the substantia nigra (SN) and striatal dopamine (DA) depletion that are reminescent of PD. The toxic effects of MPP$ sp+$ are related to the inhibition of NADH dehydrogenase activity in the mitochondrial respiratory chain. This event leads to the rapid depletion of ATP synthesis and loss of membrane potential to further enhance free radical formations. Similar respiratory deficits are reported in PD. The major antioxidant enzymes in the CNS are superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT). SOD catalyses the dismutation of superoxide (O$ sb2 sp{ cdot}$) radical into H$ sb2$O$ sb2$, while GSH-PX and CAT convert H$ sb2$O$ sb2$ to H$ sb2$O. Lipid peroxidation and SOD activity are increased in PD brains, whereas CAT and GSH-PX remain unchanged or reduced. This observation is suggestive of a deficiency in dealing with excessive H$ sb2$O$ sb2$ formation which exacerbates iron-catalysed free radical generations. To date however, it is unclear if the alteration in SOD activity observed in PD is sufficient to enhance free radical formation and, consequently, to increase lipid peroxidation. We were able to demonstrate that, despite marked alterations in SOD and CAT activities in the SN and striatum of MPTP-treated mice, lipid peroxidation remained unaffected. These results suggest that factors other than antioxidant enzymes play a pivotal role in the modulation of peroxidative damage to lipids as observed in PD. Surprisingly, L-deprenyl, a potent MAO-B inhibitor known to protect dopaminergic neurons against the deleterious effects of MPTP by blocking MPP$ sp+$ formation,

Thesis (Ph.D.)--Wake Forest University, 2007. / (UMI)AAI3294400. Source: Dissertation Abstracts International, Volume: 68-12, Section: B, page: 7973. Adviser: Michael Aschner.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0952. Adviser: Matthew A. Wallig. Includes bibliographical references (leaves 123-136) Available on microfilm from Pro Quest Information and Learning.

The presence and fate of the steroidal estrogens, estrone (E1), 17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2), in Ottawa and Cornwall wastewater treatment plants (WWTP's), drinking water, and the river water used as the drinking water source, were identified. Estrogens were extracted using accelerated solvent extraction, gel permeation chromatography and solid phase extraction, and identified using gas chromatography-mass spectrometry and internal C-13 standards. E1, E2 and EE2 concentrations ranged from 1.8 to 370, 24.3 to 66.9 and 0.4 to 9.8 ng L-1, respectively, and were affected by weather variables such as temperature and precipitation, and WWTP parameters such as daily flow and carbonaceous biochemical oxygen demand. Photodegradation rate constants under ultraviolet B radiation for E1 were directly proportional to radiation intensity and sample thickness, and inversely proportional to dissolved organic carbon concentration, but EE2 was remarkably persistent. A luciferase reporter gene assay found estrogenicity in both sewage effluent and UVB-exposed samples of estrogens, contributed by the degradation products of steroidal estrogens. Finally, EE2 persistence was also seen in a time-course experiment in which goldfish were exposed to 25 ng L-1 EE2. A mass-balance model calculated a bioconcentration factor (BCF) for EE2 in fish blood of 1400, whereas measured data revealed a maximum BCF of only 500.

Recent evidence suggests an association between persistent organic pollutants (POPs) and type 2 diabetes. In two First Nations communities of high wild food consumption, specific objectives were formulated to: (1) compare POP levels between diabetics and non-diabetics; (2) investigate the association between POPs and insulin resistance in non-diabetics; and (3) determine the effects of POPs on certain inflammatory markers. Results indicated significantly higher age-adjusted plasma concentrations of some POPs in diabetics as compared to non-diabetics. Body mass index was found to be the most significant predictor of insulin resistance. There was a positive association of Tumour Necrosis Factor (TNF)-alpha with oxychlordane and mono/di-ortho substituted polychlorinated biphenyls (PCBs). Positive associations were detected between adiponectin and mono/di-ortho substituted PCBs as well as some pesticides. Results indicate that diabetics have higher levels of some POPs than non-diabetics. In non-diabetics, POPs are unrelated to insulin resistance although some are positively associated with inflammatory markers.

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